Jack Donald Keene

Journal Article PLoS Genet · March 2023 DND1 is essential to maintain germ cell identity. Loss of Dnd1 function results in germ cell differentiation to teratomas in some inbred strains of mice or to somatic fates in zebrafish. Using our knock-in mouse line in which a functional fusion protein be ... Full text Link to item Cite

A transgenic DND1GFP fusion allele reports in vivo expression and RNA-binding targets in undifferentiated mouse germ cells†.

Journal Article Biol Reprod · April 1, 2021 In vertebrates, the RNA-binding protein (RBP) dead end 1 (DND1) is essential for primordial germ cell (PGC) survival and maintenance of cell identity. In multiple species, Dnd1 loss or mutation leads to severe PGC loss soon after specification or, in some ... Full text Link to item Cite

THE RNA BINDING PROTEIN ZFP36L1 MAINTAINS HEPATOCYTE MATURITY IN HEALTHY ADULT LIVER

Conference HEPATOLOGY · 2020 Cite

The RNA-binding protein DND1 acts sequentially as a negative regulator of pluripotency and a positive regulator of epigenetic modifiers required for germ cell reprogramming.

Journal Article Development · July 25, 2019 The adult spermatogonial stem cell population arises from pluripotent primordial germ cells (PGCs) that enter the fetal testis around embryonic day (E)10.5. PGCs undergo rapid mitotic proliferation, then enter prolonged cell cycle arrest (G1/G0), during wh ... Full text Open Access Link to item Cite

Ras Post-transcriptionally Enhances a Pre-malignantly Primed EMT to Promote Invasion.

Journal Article iScience · June 29, 2018 Epithelial-to-mesenchymal transition (EMT) is integral to cancer progression, with considerable evidence that EMT has multiple intermediary stages. Understanding the mechanisms of this stepwise activation is of great interest. We recreated a genetically de ... Full text Open Access Link to item Cite

RNA regulons in cancer and inflammation.

Journal Article Curr Opin Genet Dev · February 2018 Gene expression is the fundamental driving force that coordinates normal cellular processes and adapts to dysfunctional conditions such as oncogenic development and progression. While transcription is the basal process of gene expression, RNA transcripts a ... Full text Link to item Cite

RNA Binding Proteins Control Transdifferentiation of Hepatic Stellate Cells into Myofibroblasts.

Journal Article Cell Physiol Biochem · 2018 BACKGROUND/AIMS: Myofibroblasts (MF) derived from quiescent nonfibrogenic hepatic stellate cells (HSC) are the major sources of fibrous matrix in cirrhosis. Because many factors interact to regulate expansion and regression of MF-HSC populations, efforts t ... Full text Link to item Cite

Analysis of post-transcriptional regulation during cancer progression using a donor-derived isogenic model of tumorigenesis.

Journal Article Methods · August 15, 2017 Post-transcriptional regulation of gene expression by RNA binding proteins (RBPs) and non-coding RNAs plays an important role in global gene expression. Many post-transcriptional regulators are misexpressed and misregulated in cancers, resulting in altered ... Full text Link to item Cite

DO-RIP-seq to quantify RNA binding sites transcriptome-wide.

Journal Article Methods · April 15, 2017 Post-transcriptional processes orchestrate gene expression through dynamic protein-RNA interactions. These interactions occur at specific sites determined by RNA sequence, secondary structure, or nucleotide modifications. Methods have been developed either ... Full text Link to item Cite

Quantifying RNA binding sites transcriptome-wide using DO-RIP-seq.

Journal Article RNA · January 2017 RNA-binding proteins (RBPs) and noncoding RNAs orchestrate post-transcriptional processes through the recognition of specific sites on targeted transcripts. Thus, understanding the connection between binding to specific sites and active regulation of the w ... Full text Link to item Cite

SHAPE reveals transcript-wide interactions, complex structural domains, and protein interactions across the Xist lncRNA in living cells.

Journal Article Proc Natl Acad Sci U S A · September 13, 2016 The 18-kb Xist long noncoding RNA (lncRNA) is essential for X-chromosome inactivation during female eutherian mammalian development. Global structural architecture, cell-induced conformational changes, and protein-RNA interactions within Xist are poorly un ... Full text Link to item Cite

Functional coordination and HuR-mediated regulation of mRNA stability during T cell activation.

Journal Article Nucleic Acids Res · January 8, 2016 Global mRNA abundance depends on the balance of synthesis and decay of a population of mRNAs. To account for this balance during activation of T cells, we used metabolic labeling to quantify the contributions of RNA transcription and decay over a 4 h time ... Full text Open Access Link to item Cite

Abstract P6-07-06: Post-transcriptional coordination of gene expression during breast cancer tumorigenesis

Conference Cancer Research · May 1, 2015 AbstractWe investigate mechanisms of RNA regulation central to human breast cancer progression. Aberrant gene expression is known to be an important factor in cancer, yet little is known about the role RNA-b ... Full text Cite

XRN1 stalling in the 5' UTR of Hepatitis C virus and Bovine Viral Diarrhea virus is associated with dysregulated host mRNA stability.

Journal Article PLoS Pathog · March 2015 We demonstrate that both Hepatitis C virus (HCV) and Bovine Viral Diarrhea virus (BVDV) contain regions in their 5' UTRs that stall and repress the enzymatic activity of the cellular 5'-3' exoribonuclease XRN1, resulting in dramatic changes in the stabilit ... Full text Link to item Cite

Coordinating expression of RNA binding proteins with their mRNA targets.

Journal Article Sci Rep · November 24, 2014 Post-transcriptional regulation by RNA binding proteins (RBPs) plays prominent roles in a variety of biological processes. In this study, by analyzing the global regulatory relationship between RBPs and their target mRNAs in yeast, we discovered that most ... Full text Link to item Cite

Post-transcriptional RNA regulons affecting cell cycle and proliferation.

Journal Article Semin Cell Dev Biol · October 2014 The cellular growth cycle is initiated and maintained by punctual, yet agile, regulatory events involving modifications of cell cycle proteins as well as coordinated gene expression to support cyclic checkpoint decisions. Recent evidence indicates that pos ... Full text Link to item Cite

Transcriptional and posttranscriptional regulation of cytokine gene expression in HIV-1 antigen-specific CD8+ T cells that mediate virus inhibition.

Journal Article J Virol · September 1, 2014 UNLABELLED: The ability of CD8+ T cells to effectively limit HIV-1 replication and block HIV-1 acquisition is determined by the capacity to rapidly respond to HIV-1 antigens. Understanding both the functional properties and regulation of an effective CD8+ ... Full text Link to item Cite

The globalization of messenger RNA regulation.

Journal Article Natl Sci Rev · June 2014 Full text Link to item Cite

Advancing the functional utility of PAR-CLIP by quantifying background binding to mRNAs and lncRNAs.

Journal Article Genome Biol · January 7, 2014 BACKGROUND: Sequence specific RNA binding proteins are important regulators of gene expression. Several related crosslinking-based, high-throughput sequencing methods, including PAR-CLIP, have recently been developed to determine direct binding sites of gl ... Full text Link to item Cite

Mechanisms coordinating ELAV/Hu mRNA regulons.

Journal Article Curr Opin Genet Dev · February 2013 The 5' and 3' untranslated regions (UTRs) of messenger RNAs (mRNAs) function as platforms that can determine the fate of each mRNA individually and in aggregate. Multiple mRNAs that encode proteins that are functionally related often interact with RNA-bind ... Full text Link to item Cite

Ten Years of Progress in GW/P Body Research Preface

Chapter · January 1, 2013 Link to item Cite

Neuron-specific ELAV/Hu proteins suppress HuR mRNA during neuronal differentiation by alternative polyadenylation.

Journal Article Nucleic Acids Res · March 2012 The ubiquitously expressed RNA-binding protein HuR increases the stability and translation of mRNAs encoding growth regulatory proteins that promote proliferation in a variety of cell types. However, the three neuron-specific ELAV/Hu proteins, HuB, HuC and ... Full text Link to item Cite

Preface

Journal Article Current Topics in Behavioral Neurosciences · December 1, 2011 Cite

PARalyzer: definition of RNA binding sites from PAR-CLIP short-read sequence data.

Journal Article Genome Biol · August 18, 2011 Crosslinking and immunoprecipitation (CLIP) protocols have made it possible to identify transcriptome-wide RNA-protein interaction sites. In particular, PAR-CLIP utilizes a photoactivatable nucleoside for more efficient crosslinking. We present an approach ... Full text Link to item Cite

Integrative regulatory mapping indicates that the RNA-binding protein HuR couples pre-mRNA processing and mRNA stability.

Journal Article Mol Cell · August 5, 2011 RNA-binding proteins coordinate the fates of multiple RNAs, but the principles underlying these global interactions remain poorly understood. We elucidated regulatory mechanisms of the RNA-binding protein HuR, by integrating data from diverse high-throughp ... Full text Open Access Link to item Cite

ATM regulates a DNA damage response posttranscriptional RNA operon in lymphocytes.

Journal Article Blood · February 24, 2011 Maintenance of genomic stability depends on the DNA damage response, a biologic barrier in early stages of cancer development. Failure of this response results in genomic instability and high predisposition toward lymphoma, as seen in patients with ataxia- ... Full text Link to item Cite

Tissue type-specific expression of the dsRNA-binding protein 76 and genome-wide elucidation of its target mRNAs.

Journal Article PLoS One · July 23, 2010 BACKGROUND: RNA-binding proteins accompany all steps in the life of mRNAs and provide dynamic gene regulatory functions for rapid adjustment to changing extra- or intracellular conditions. The association of RNA-binding proteins with their targets is regul ... Full text Open Access Link to item Cite

The global dynamics of RNA stability orchestrates responses to cellular activation.

Journal Article BMC Biol · July 8, 2010 Transcriptomics is used to quantify changes in accumulated levels of mRNAs following cellular activation. These changes arise from the opposing fluxes of transcription and mRNA decay, both of which affect the functional dynamics of global gene expression. ... Full text Link to item Cite

Minireview: global regulation and dynamics of ribonucleic Acid.

Journal Article Endocrinology · April 2010 Gene expression starts with transcription and is followed by multiple posttranscriptional processes that carry out the splicing, capping, polyadenylation, and export of each mRNA. Interest in posttranscriptional regulation has increased recently with explo ... Full text Link to item Cite

Systematic analysis of posttranscriptional gene expression.

Journal Article Wiley Interdiscip Rev Syst Biol Med · 2010 Recent systems studies of gene expression have begun to dissect the layers of regulation that underlie the eukaryotic transcriptome, the combined consequence of transcriptional and posttranscriptional events. Among the regulatory layers of the transcriptom ... Full text Link to item Cite

Control of thymic T cell maturation, deletion and egress by the RNA-binding protein HuR.

Journal Article J Immunol · June 1, 2009 HuR emerged as a posttranscriptional regulator of mRNAs involved in cellular control, stress, and immunity but its role in governing such responses remains elusive. In this study, we assessed HuR's role in the staged progression of thymic T cell differenti ... Full text Link to item Cite

Proteomic and immunologic analyses of brain tumor exosomes.

Journal Article FASEB J · May 2009 Brain tumors are horrific diseases with almost universally fatal outcomes; new therapeutics are desperately needed and will come from improved understandings of glioma biology. Exosomes are endosomally derived 30-100 nm membranous vesicles released from ma ... Full text Link to item Cite

The ribonome: a dominant force in co-ordinating gene expression.

Journal Article Biol Cell · March 2009 The ribonome is the total cellular complement of RNAs and their regulatory factors functioning dynamically in time and space within ribonucleoprotein complexes. We theorize that the ribonome is an ancient central co-ordinator that has evolved to communicat ... Full text Link to item Cite

Coordinated posttranscriptional mRNA population dynamics during T-cell activation.

Journal Article Mol Syst Biol · 2009 Although RNA-binding proteins (RBPs) coordinate many key decisions during cell growth and differentiation, the dynamics of RNA-RBP interactions have not been extensively studied on a global basis. We immunoprecipitated endogenous ribonucleoprotein complexe ... Full text Link to item Cite

Activity-dependent expression of ELAV/Hu RBPs and neuronal mRNAs in seizure and cocaine brain.

Journal Article J Neurochem · December 2008 Growing evidence indicates that both seizure (glutamate) and cocaine (dopamine) treatment modulate synaptic plasticity within the mesolimbic region of the CNS. Activation of glutamatergic neurons depends on the localized translation of neuronal mRNA produc ... Full text Link to item Cite

Post-transcriptional gene regulation by HuR promotes a more tumorigenic phenotype.

Journal Article Oncogene · October 16, 2008 In a breast tumor xenograft model, the MCT-1 oncogene increases the in vivo tumorgenicity of MCF7 cells by promoting angiogenesis and inhibiting apoptosis. Increases in the tumor microvascular density are accompanied by a strong reduction in the levels of ... Full text Link to item Cite

Ribonomic analysis of human Pum1 reveals cis-trans conservation across species despite evolution of diverse mRNA target sets.

Journal Article Mol Cell Biol · June 2008 PUF family proteins are among the best-characterized regulatory RNA-binding proteins in nonmammalian species, but relatively little is known about mRNA targets or functions of mammalian PUF proteins. In this study, we used ribonomic analysis to identify an ... Full text Link to item Cite

Signal sequence- and translation-independent mRNA localization to the endoplasmic reticulum.

Journal Article RNA · March 2008 The process of mRNA localization typically utilizes cis-targeting elements and trans-recognition factors to direct the compartmental organization of translationally suppressed mRNAs. mRNA localization to the endoplasmic reticulum (ER), in contrast, occurs ... Full text Link to item Cite

Caspase-mediated cleavage of HuR in the cytoplasm contributes to pp32/PHAP-I regulation of apoptosis.

Journal Article J Cell Biol · January 14, 2008 The RNA-binding protein HuR affects cell fate by regulating the stability and/or the translation of messenger RNAs that encode cell stress response proteins. In this study, we delineate a novel regulatory mechanism by which HuR contributes to stress-induce ... Full text Link to item Cite

Activity-dependent expression of RNA binding protein HuD and its association with mRNAs in neurons.

Journal Article RNA Biol · 2008 The dendritic trafficking of RNA binding proteins (RBPs) is an important posttranscriptional process involved in the regulation of synaptic plasticity. For example, HuD RBP binds to AU-rich elements (AREs) in the 3' untranslated regions (3'UTR) of immediat ... Full text Link to item Cite

Ribotrap : targeted purification of RNA-specific RNPs from cell lysates through immunoaffinity precipitation to identify regulatory proteins and RNAs.

Journal Article Methods Mol Biol · 2008 Many elegant methodologies have been devised to explore RNA-protein as well as RNA-RNA interactions. Although the characterization of messages targeted by a specific RNA-binding protein (RBP) has been accelerated by the application of microarray technologi ... Full text Link to item Cite

A two-phase innate host response to alphavirus infection identified by mRNP-tagging in vivo.

Journal Article PLoS Pathog · December 2007 A concept fundamental to viral pathogenesis is that infection induces specific changes within the host cell, within specific tissues, or within the entire animal. These changes are reflected in a cascade of altered transcription patterns evident during inf ... Full text Link to item Cite

RNA regulons: coordination of post-transcriptional events.

Journal Article Nat Rev Genet · July 2007 Recent findings demonstrate that multiple mRNAs are co-regulated by one or more sequence-specific RNA-binding proteins that orchestrate their splicing, export, stability, localization and translation. These and other observations have given rise to a model ... Full text Link to item Cite

Biological Clocks and the Coordination Theory of RNA Operons and Regulons

Conference CLOCKS AND RHYTHMS · 2007 Cite

A two-phase innate host response to alphavirus infection identified by mRNP-tagging in vivo

Journal Article PLoS Pathogens · 2007 A concept fundamental to viral pathogenesis is that infection induces specific changes within the host cell, within specific tissues, or within the entire animal. These changes are reflected in a cascade of altered transcription patterns evident during inf ... Full text Cite

Biological clocks and the coordination theory of RNA operons and regulons.

Journal Article Cold Spring Harb Symp Quant Biol · 2007 One of the regulatory models of circadian rhythms involves the oscillation of transcription and translation. Although transcription factors have been widely examined during circadian processes, posttranscriptional mechanisms are less well-studied. Several ... Full text Link to item Cite

Erratum: RIP-Chip: The isolation and identification of mRNAs, microRNAS and protein components of ribonucleoprotein complexes from cell extracts (Nature Protocols (2006) vol. 1 (302-307) 10.1038/nprot.2006.47)

Journal Article Nature Protocols · June 1, 2006 Cite

RIP-Chip: the isolation and identification of mRNAs, microRNAs and protein components of ribonucleoprotein complexes from cell extracts.

Journal Article Nat Protoc · 2006 RNA targets of multitargeted RNA-binding proteins (RBPs) can be studied by various methods including mobility shift assays, iterative in vitro selection techniques and computational approaches. These techniques, however, cannot be used to identify the cell ... Full text Link to item Cite

Stable ribosome binding to the endoplasmic reticulum enables compartment-specific regulation of mRNA translation.

Journal Article Mol Biol Cell · December 2005 In eukaryotic cells, protein synthesis is compartmentalized; mRNAs encoding secretory/membrane proteins are translated on endoplasmic reticulum (ER)-bound ribosomes, whereas mRNAs encoding cytosolic proteins are translated on free ribosomes. mRNA partition ... Full text Link to item Cite

Erratum: Posttranscriptional operons and regulons coordinating gene expression (Chromosome Research (2005) 13:3 (327-337))

Journal Article Chromosome Research · June 1, 2005 Cite

Post-transcriptional operons and regulons co-ordinating gene expression.

Journal Article Chromosome Res · 2005 Experiments reported over the past several years, including genome-wide microarray approaches, have demonstrated that many eukaryotic RNA-binding proteins (RBPs) associate with multiple messenger RNAs (mRNAs) both in vitro and in vivo. This multi-targeted ... Full text Link to item Cite

Biotinylated tags for recovery and characterization of ribonucleoprotein complexes.

Journal Article Biotechniques · October 2004 Determining the in vivo targets of RNA-binding proteins and characterizing the posttranscriptional networks in which they participate constitute major challenges in the post-genomic era. An important step in this direction is the development of methods tha ... Full text Link to item Cite

RNA-binding proteins to assess gene expression states of co-cultivated cells in response to tumor cells.

Journal Article Mol Cancer · September 7, 2004 BACKGROUND: Tumors and complex tissues consist of mixtures of communicating cells that differ significantly in their gene expression status. In order to understand how different cell types influence one another's gene expression, it will be necessary to mo ... Full text Link to item Cite

Search for organising principles: understanding in systems biology.

Journal Article Syst Biol (Stevenage) · June 2004 Due in large measure to the explosive progress in molecular biology, biology has become arguably the most exciting scientific field. The first half of the 21st century is sometimes referred to as the 'era of biology', analogous to the first half of the 20t ... Full text Link to item Cite

Microbiology and Molecular Biology Reviews: Note from the editor in chief

Journal Article Microbiology and Molecular Biology Reviews · June 1, 2004 Cite

La gets its wings.

Journal Article Nat Struct Mol Biol · April 2004 Full text Link to item Cite

Gene expression analysis of messenger RNP complexes.

Journal Article Methods Mol Biol · 2004 RNA-binding proteins can organize messenger RNAs (mRNAs) into structurally and functionally related subsets, thus facilitating the coordinate production of gene classes necessary for complex cellular processes. Historically, in vitro methods primarily have ... Full text Link to item Cite

Preface

Journal Article Supplements to Clinical Neurophysiology · January 1, 2004 Full text Cite

Posttranscriptional generation of macromolecular complexes.

Journal Article Mol Cell · December 2003 Discrete classes of mRNAs that encode functionally related proteins are associated with sequence-specific RNA-binding proteins in yeast and mammalian cells. recently reported that pre-mRNAs encoding components of inhibitory synapses are bound to neuron-spe ... Full text Link to item Cite

Differential phosphorylation and subcellular localization of La RNPs associated with precursor tRNAs and translation-related mRNAs.

Journal Article Mol Cell · November 2003 The La protein facilitates the production of tRNAs in the nucleus and the translation of specific mRNAs in the cytoplasm. We report that human La that is phosphorylated on serine 366 (pLa) is nucleoplasmic and associated with precursor tRNAs and other nasc ... Full text Link to item Cite

Genome-wide regulatory analysis using en masse nuclear run-ons and ribonomic profiling with autoimmune sera.

Journal Article Gene · October 23, 2003 Coordinated gene expression is influenced by transcriptional and posttranscriptional events and is necessary for efficient cell growth and differentiation. Genomic array technologies have afforded great advances in identifying global changes of gene expres ... Full text Link to item Cite

Partitioning and translation of mRNAs encoding soluble proteins on membrane-bound ribosomes.

Journal Article RNA · September 2003 In eukaryotic cells, it is generally accepted that protein synthesis is compartmentalized; soluble proteins are synthesized on free ribosomes, whereas secretory and membrane proteins are synthesized on endoplasmic reticulum (ER)-bound ribosomes. The partit ... Full text Link to item Cite

RNA-binding protein HuR enhances p53 translation in response to ultraviolet light irradiation.

Journal Article Proc Natl Acad Sci U S A · July 8, 2003 Exposure to short-wavelength UV light (UVC) strongly induces p53 expression. In human RKO colorectal carcinoma cells, this increase was not due to elevated p53 mRNA abundance, cytoplasmic export of p53 mRNA, or UVC-triggered stabilization of the p53 protei ... Full text Link to item Cite

Organizing mRNA export.

Journal Article Nat Genet · February 2003 Full text Link to item Cite

Eukaryotic mRNPs may represent posttranscriptional operons.

Journal Article Mol Cell · June 2002 Genomic array analysis of endogenous mammalian ribonucleoproteins has recently revealed three novel findings: (1) mRNA binding proteins are associated with unique subpopulations of messages, (2) the compositions of these mRNA subsets can vary with growth c ... Full text Link to item Cite

Autoimmune epitopes in messenger RNA.

Journal Article RNA · June 2002 Patients with systemic autoimmune disorders produce autoantibodies against sequence-specific conformational RNA epitopes on U1 snRNA, 28S rRNA, and transfer RNAs. The molecular basis for immunological reactivity with these highly abundant and stable RNAs i ... Full text Link to item Cite

A phosphorylated cytoplasmic autoantigen, GW182, associates with a unique population of human mRNAs within novel cytoplasmic speckles.

Journal Article Mol Biol Cell · April 2002 A novel human cellular structure has been identified that contains a unique autoimmune antigen and multiple messenger RNAs. This complex was discovered using an autoimmune serum from a patient with motor and sensory neuropathy and contains a protein of 182 ... Full text Link to item Cite

Ribonomics: identifying mRNA subsets in mRNP complexes using antibodies to RNA-binding proteins and genomic arrays.

Journal Article Methods · February 2002 Although in vitro methods have been used to identify putative targets of mRNA-binding proteins, direct in vivo methods are needed to identify endogenously associated mRNAs and their cognate proteins. Therefore, we have developed high-throughput methods to ... Full text Link to item Cite

Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome.

Journal Article Cell · November 16, 2001 Fragile X syndrome results from the absence of the RNA binding FMR protein. Here, mRNA was coimmunoprecipitated with the FMRP ribonucleoprotein complex and used to interrogate microarrays. We identified 432 associated mRNAs from mouse brain. Quantitative R ... Full text Link to item Cite

Ribonucleoprotein infrastructure regulating the flow of genetic information between the genome and the proteome.

Journal Article Proc Natl Acad Sci U S A · June 19, 2001 Following transcription and splicing, each mRNA of a mammalian cell passes into the cytoplasm where its fate is in the hands of a complex network of ribonucleoproteins (mRNPs). The success or failure of a gene to be expressed depends on the performance of ... Full text Link to item Cite

Identifying mRNA subsets in messenger ribonucleoprotein complexes by using cDNA arrays.

Journal Article Proc Natl Acad Sci U S A · December 19, 2000 Genomic array technologies provide a means for profiling global changes in gene expression under a variety of conditions. However, it has been difficult to assess whether transcriptional or posttranscriptional regulation is responsible for these changes. A ... Full text Link to item Cite

Human La antigen is required for the hepatitis C virus internal ribosome entry site-mediated translation.

Journal Article J Biol Chem · September 8, 2000 The 5'-noncoding region (5'-NCR) of the hepatitis C virus (HCV) RNA genome serves as an internal ribosome entry site (IRES) and mediates translation initiation in a cap-independent manner. Previously, we reported the interaction between La antigen and the ... Full text Link to item Cite

Inhibition of polyglutamine protein aggregation and cell death by novel peptides identified by phage display screening.

Journal Article J Biol Chem · April 7, 2000 Proteins with expanded polyglutamine domains cause eight inherited neurodegenerative diseases, including Huntington's, but the molecular mechanism(s) responsible for neuronal degeneration are not yet established. Expanded polyglutamine domain proteins poss ... Full text Link to item Cite

Identification of QBP1, a synthetic peptide that preferentially binds expanded polyglutamine domain by phage display technique.

Journal Article AMERICAN JOURNAL OF HUMAN GENETICS · October 1, 1999 Link to item Cite

ELAV tumor antigen, Hel-N1, increases translation of neurofilament M mRNA and induces formation of neurites in human teratocarcinoma cells.

Journal Article Genes Dev · February 15, 1999 Human ELAV proteins are implicated in cell growth and differentiation via regulation of mRNA expression in the cytoplasm. In human embryonic teratocarcinoma (hNT2) cells transfected with the human neuronal ELAV-like protein, Hel-N1, neurites formed, yet ce ... Full text Link to item Cite

ELAV proteins stabilize deadenylated intermediates in a novel in vitro mRNA deadenylation/degradation system.

Journal Article Genes Dev · January 15, 1999 We have developed an in vitro mRNA stability system using HeLa cell cytoplasmic S100 extracts and exogenous polyadenylated RNA substrates that reproduces regulated aspects of mRNA decay. The addition of cold poly(A) competitor RNA activated both a sequence ... Full text Link to item Cite

Why is Hu where? Shuttling of early-response-gene messenger RNA subsets.

Journal Article Proc Natl Acad Sci U S A · January 5, 1999 Full text Link to item Cite

In vitro selection of aptamers from RNA libraries.

Journal Article Methods Mol Biol · 1999 Full text Link to item Cite

Identification of specific protein-RNA target sites using libraries of natural sequences.

Journal Article Methods Mol Biol · 1999 Full text Link to item Cite

ELAV protein HuA (HuR) can redistribute between nucleus and cytoplasm and is upregulated during serum stimulation and T cell activation.

Journal Article J Cell Sci · November 1998 ELAV proteins are implicated in regulating the stability and translation of cytokine and growth regulatory mRNAs such as GM-CSF, IL-2, c-myc, c-fos and GLUT1 by binding to their AU-rich 3'UTRs. The tissue-specific ELAV protein HuB (aka. Hel-N1) is predomin ... Full text Link to item Cite

Combinatorial chemistry.

Journal Article Curr Biol · October 8, 1998 Full text Link to item Cite

Messenger ribonucleoprotein complexes containing human ELAV proteins: interactions with cytoskeleton and translational apparatus.

Journal Article Journal of cell science · January 1998 Mammalian ELAV proteins bind to polyadenylated messenger RNAs and have specificity for AU-rich sequences. Preferred binding sites in vitro include the AUUUA pentamer and related sequences present in the 3' untranslated regions of many growth regulatory mRN ... Full text Cite

Embryonic lethal abnormal visual RNA-binding proteins involved in growth, differentiation, and posttranscriptional gene expression.

Journal Article Am J Hum Genet · August 1997 Full text Link to item Cite

Ectopic expression of Hel-N1, an RNA-binding protein, increases glucose transporter (GLUT1) expression in 3T3-L1 adipocytes.

Journal Article Mol Cell Biol · February 1997 3T3-L1 preadipocytes ectopically expressing the mammalian RNA-binding protein Hel-N1 expressed up to 10-fold more glucose transporter (GLUT1) protein and exhibited elevated rates of basal glucose uptake. Hel-N1 is a member of the ELAV-like family of protei ... Full text Link to item Cite

Letters

Journal Article Scientist · August 19, 1996 Cite

RNA surfaces as functional mimetics of proteins.

Journal Article Chem Biol · July 1996 Accumulating evidence suggests that RNA molecules can form surfaces that mimic those of proteins. Reactivity of autoantibodies with RNA surfaces may be due to cross-reactivity between a protein epitope and the RNA. The structural mimicry detected by an aut ... Full text Link to item Cite

Hel-N1/Hel-N2 proteins are bound to poly(A)+ mRNA in granular RNP structures and are implicated in neuronal differentiation.

Journal Article J Cell Sci · March 1996 Human proteins Hel-N1 and Hel-N2 contain three RNA recognition motifs (RRMs), and are members of a family of proteins highly homologous to Drosophila ELAV, which is essential for neuronal differentiation. Both proteins bind to A+U-rich 3' untranslated regi ... Full text Link to item Cite

Sequences within a small yeast RNA required for inhibition of internal initiation of translation: interaction with La and other cellular proteins influences its inhibitory activity.

Journal Article J Virol · March 1996 We recently reported purification, determination of the nucleotide sequence, and cloning of a 60-nucleotide RNA (I-RNA) from the yeast Saccharomyces cerevisiae which preferentially blocked cap-independent, internal ribosome entry site (IRES)-mediated trans ... Full text Link to item Cite

RNA recognition by autoantigens and autoantibodies.

Journal Article Mol Biol Rep · 1996 The La, Ro, Sm and RNP autoantigens have been intensely studied over the past decade since cDNAs encoding autoantigens have been available. Most of these autoantigens are closely associated with RNA in RNP particles and molecular studies have provided insi ... Full text Link to item Cite

Randomization and selection of RNA to identify targets for RRM RNA-binding proteins and antibodies.

Journal Article Methods Enzymol · 1996 Full text Link to item Cite

In vitro RNA selection identifies RNA ligands that specifically bind to eukaryotic translation initiation factor 4B: the role of the RNA remotif.

Journal Article RNA · January 1996 Translation initiation factor elF-4B is an RNA-binding protein that promotes the association of the mRNA to the 40S ribosomal subunit. One of its better characterized features is the ability to stimulate the activity of the DEAD box RNA hilicase elF-4A. In ... Link to item Cite

Overexpression of the arginine-rich carboxy-terminal region of U1 snRNP 70K inhibits both splicing and nucleocytoplasmic transport of mRNA.

Journal Article Genes Dev · June 1, 1995 Transient transfection of the U1 snRNP 70K protein into COS cells induced nuclear reorganization and redistribution of the splicing factor SC-35, whereas hnRNP proteins were not affected. Correspondingly, splicing and nucleocytoplasmic transport of a coexp ... Full text Link to item Cite

Hel-N1, an RNA-binding protein, is a ligand for an A + U rich region of the GLUT1 3' UTR.

Journal Article Nucleic Acids Symp Ser · 1995 Hel-N1, is an RRM protein which is a mammalian homologue of the Drosophila melanogaster RNA binding protein, ELAV (embryonic lethal abnormal vision). Hel-N1 binds to RNA containing short stretches of uridylates similar to those found in the 3' untranslated ... Link to item Cite

Direct interactions between autoantigen La and human immunodeficiency virus leader RNA.

Journal Article J Virol · January 1995 Full text Link to item Cite

Selection of a subset of mRNAs from combinatorial 3' untranslated region libraries using neuronal RNA-binding protein Hel-N1.

Journal Article Proc Natl Acad Sci U S A · November 8, 1994 Hel-N1, a human RNA-binding protein, shares significant homology with Drosophila protein ELAV, which is essential for fly neuronal development. Hel-N1 has been shown to bind in vitro to 3' untranslated regions of mRNAs encoding c-myc, c-fos, granulocyte/ma ... Full text Link to item Cite

Direct interactions between autoantigen La and human immunodeficiency virus leader RNA.

Journal Article J Virol · November 1994 We have characterized the in vivo and in vitro binding of human La protein to the human immunodeficiency virus type 1 (HIV-1) leader RNA, the trans-activation response element (TAR). In immunoprecipitation studies using anti-La serum, La-TAR ribonucleoprot ... Full text Link to item Cite

The U1 small nuclear ribonucleoprotein (snRNP) 70K protein is transported independently of U1 snRNP particles via a nuclear localization signal in the RNA-binding domain.

Journal Article Mol Cell Biol · July 1994 Expression of the recombinant human U1-70K protein in COS cells resulted in its rapid transport to the nucleus, even when binding to U1 RNA was debilitated. Deletion analysis of the U1-70K protein revealed the existence of two segments of the protein which ... Full text Link to item Cite

60-kDa Ro protein autoepitopes identified using recombinant polypeptides.

Journal Article J Immunol · April 15, 1994 The human Ro ribonucleoprotein is a clinically important yet poorly understood autoantigen. The contribution of Ro autoantibodies to pathogenesis of autoimmune disease remains unclear, as do the stimuli that initiate and maintain the response. Recent evide ... Link to item Cite

Mammalian homologs of Drosophila ELAV localized to a neuronal subset can bind in vitro to the 3' UTR of mRNA encoding the Id transcriptional repressor.

Journal Article J Neurosci · April 1994 Mammalian cDNAs encoding a rat (Rel-N1) and a human (Hel-N1) neuronal RNA-binding protein have been cloned and characterized with respect to tissue specificity, neuroanatomical localization, and RNA binding specificity. Both proteins are highly similar to ... Full text Link to item Cite

Molecular composition of Ro small ribonucleoprotein complexes in human cells. Intracellular localization of the 60- and 52-kD proteins.

Journal Article J Clin Invest · April 1994 Ro small ribonucleoprotein complexes (RoRNPs) are thought to comprise several proteins, including the 60-kD Ro and the 52-kD Ro proteins, and several small RNAs, designated Y RNAs. Although RoRNPs are fairly ubiquitous in nature, their precise composition ... Full text Link to item Cite

Eukaryotic transcription termination factor La mediates transcript release and facilitates reinitiation by RNA polymerase III.

Journal Article Mol Cell Biol · March 1994 Ample evidence indicates that Alu family interspersed elements retrotranspose via primary transcripts synthesized by RNA polymerase III (pol III) and that this transposition sometimes results in genetic disorders in humans. However, Alu primary transcripts ... Full text Link to item Cite

Exploring molecular diversity with combinatorial shape libraries.

Journal Article Trends Biochem Sci · February 1994 Surface technologies based upon selection of ligands from combinatorial libraries herald a revolution in molecular research and drug discovery. Molecular diversity is generated by random combinations of monomeric building blocks to form polymeric conformer ... Full text Link to item Cite

La autoantigen enhances and corrects aberrant translation of poliovirus RNA in reticulocyte lysate.

Journal Article J Virol · July 1993 Translation initiation on poliovirus RNA occurs by internal binding of ribosomes to a sequence within the 5' untranslated region. We have previously characterized a HeLa cell protein, p52, that binds to a fragment of the poliovirus 5' untranslated region ( ... Full text Link to item Cite

Hel-N1: an autoimmune RNA-binding protein with specificity for 3' uridylate-rich untranslated regions of growth factor mRNAs.

Journal Article Mol Cell Biol · June 1993 We have investigated the RNA binding specificity of Hel-N1, a human neuron-specific RNA-binding protein, which contains three RNA recognition motifs. Hel-N1 is a human homolog of Drosophila melanogaster elav, which plays a vital role in the development of ... Full text Link to item Cite

In vitro selection of RNA epitopes using autoimmune patient serum.

Journal Article J Immunol · February 1, 1993 Nucleotide-specific autoimmune epitopes have not been precisely defined despite the fact that certain kinds of DNA and RNA species are known to bind autoantibodies. Our laboratory has used nucleic acid epitope libraries, consisting of randomized RNA pools, ... Link to item Cite

In vitro selection of an RNA epitope immunologically cross-reactive with a peptide.

Journal Article Proc Natl Acad Sci U S A · October 1, 1992 An antiserum raised against a peptide was used to select a unique RNA species from a degenerate pool of RNAs designed to resemble an autoantibody recognition site in U1 RNA. The peptide and the selected RNA epitope could compete for antibody binding, sugge ... Full text Link to item Cite

INVITRO SELECTION OF DOUBLE-STRANDED DNA-MOLECULES THAT BIND AN ANTI-DNA ANTIBODY

Conference ARTHRITIS AND RHEUMATISM · September 1, 1992 Link to item Cite

RNA binding specificity of a Drosophila snRNP protein that shares sequence homology with mammalian U1-A and U2-B" proteins.

Journal Article Nucleic Acids Res · July 25, 1992 We have characterized a recombinant Drosophila melanogaster RNA binding protein, D25, by virtue of its antigenic relationship to mammalian U1 and U2 small nuclear ribonucleoprotein (U snRNP) proteins. Sequence analysis revealed that D25 bears strong simila ... Full text Link to item Cite

Molecular biology of nuclear autoantigens.

Journal Article Rheum Dis Clin North Am · May 1992 This article provides a historical overview of the application of molecular and immunologic techniques to the analysis of autoantigenic structure and function, as well as to autoantibody recognition of protein and nucleic acid autoantigens. Examples presen ... Link to item Cite

U1-snRNP-A protein selects a ten nucleotide consensus sequence from a degenerate RNA pool presented in various structural contexts.

Journal Article Nucleic Acids Res · September 25, 1991 The U1snRNP-A (U1-A) protein was used to select specific RNA sequences from a degenerate pool of transcripts using direct RNA binding and polymerase chain reaction amplification (PCR). Sequences were randomized in loops of 10 or 13 nucleotides or as a line ... Full text Link to item Cite

RNA recognition: towards identifying determinants of specificity.

Journal Article Trends Biochem Sci · June 1991 Members of a family of proteins containing a conserved approximately 80-amino acid RNA recognition motif (RRM) bind specifically to a wide variety of RNA molecules. Structural studies, in combination with sequence alignments, indicate the structural contex ... Full text Link to item Cite

Recognition of U1 and U2 small nuclear RNAs can be altered by a 5-amino-acid segment in the U2 small nuclear ribonucleoprotein particle (snRNP) B" protein and through interactions with U2 snRNP-A' protein.

Journal Article Mol Cell Biol · April 1991 We have investigated the sequence elements influencing RNA recognition in two closely related small nuclear ribonucleoprotein particle (snRNP) proteins, U1 snRNP-A and U2 snRNP-B". A 5-amino-acid segment in the RNA-binding domain of the U2 snRNP-B" protein ... Full text Link to item Cite

Anti-La antibody production by MRL-1pr/1pr mice. Analysis of fine specificity.

Journal Article J Immunol · March 15, 1991 In evaluating the origin of autoantibodies, patterns of self-Ag recognition have been interpreted to reflect the relative role of Ag in stimulating a response. Few studies, however, have assessed whether human autoantibodies display patterns of autoantigen ... Link to item Cite

RNA-binding domain of the A protein component of the U1 small nuclear ribonucleoprotein analyzed by NMR spectroscopy is structurally similar to ribosomal proteins.

Journal Article Proc Natl Acad Sci U S A · March 15, 1991 An RNA recognition motif (RRM) of approximately 80 amino acids constitutes the core of RNA-binding domains found in a large family of proteins involved in RNA processing. The U1 RNA-binding domain of the A protein component of the human U1 small nuclear ri ... Full text Link to item Cite

Leucine periodicity of U2 small nuclear ribonucleoprotein particle (snRNP) A' protein is implicated in snRNP assembly via protein-protein interactions.

Journal Article Mol Cell Biol · March 1991 Recombinant A' protein could be reconstituted into U2 small nuclear ribonucleoprotein particles (snRNPs) upon addition to HeLa cell extracts as determined by coimmunoprecipitation and particle density; however, direct binding to U2 RNA could not be demonst ... Full text Link to item Cite

Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites.

Journal Article Nucleic Acids Res · January 11, 1991 Camptothecin (CPT), a plant alkaloid with antitumor activity, is a specific inhibitor of eukaryotic DNA topoisomerase I. We have previously isolated and characterized a CPT-resistant topoisomerase I isolated from a CPT-resistant human leukemia cell line, C ... Full text Link to item Cite

Nuclear RNA-binding proteins.

Journal Article Prog Nucleic Acid Res Mol Biol · 1991 Full text Link to item Cite

A three allele TaqI polymorphism at TOP1 gene.

Journal Article Nucleic Acids Res · October 11, 1990 Full text Link to item Cite

Quantitative determination that one of two potential RNA-binding domains of the A protein component of the U1 small nuclear ribonucleoprotein complex binds with high affinity to stem-loop II of U1 RNA.

Journal Article Proc Natl Acad Sci U S A · August 1990 Many RNA-associated proteins contain a ribonucleoprotein (RNP) consensus octamer encompassed by a conserved 80 amino acid sequence, which we have termed an RNA recognition motif (RRM). RRM family members contain either one (class I) or multiple (class II) ... Full text Link to item Cite

The fine specificity of anti-La antibodies induced in mice by immunization with recombinant human La autoantigen.

Journal Article J Immunol · May 15, 1990 Because of increasing evidence suggesting that anti-La autoantibodies are induced in humans by an Ag-specific mechanism, we investigated the antibody response of animals immunized with the human La Ag and studied its relationship to the anti-La response of ... Link to item Cite

SPONTANEOUS ANTI-LA ANTIBODY-PRODUCTION BY MRL-LPR/LPR MICE

Conference CLINICAL RESEARCH · April 1, 1990 Link to item Cite

THE FINE SPECIFICITY OF ANTI-LA ANTIBODIES INDUCED IN MICE BY IMMUNIZATION WITH RECOMBINANT HUMAN LA AUTOANTIGEN

Conference CLINICAL RESEARCH · April 1, 1990 Link to item Cite

Expression of autoantibodies to recombinant (U1) RNP-associated 70K antigen in systemic lupus erythematosus.

Journal Article Clin Immunol Immunopathol · February 1990 To determine the specificity of antibodies to the (U1) ribonucleoprotein antigen in systemic lupus erythematosus (SLE), patient sera were tested for binding to a recombinant human 70K antigen. By solid-phase immunoassay, we detected anti-70K reactivity in ... Full text Link to item Cite

Temporal correlation of antibody responses to different epitopes of the human La autoantigen.

Journal Article J Clin Invest · February 1990 To investigate the temporal relationship of antibody responses to different La epitopes, sequential sera from nine patients with systemic lupus erythematosus and Sjogren's syndrome were tested by enzyme-linked immunosorbent assay for antibody binding to a ... Full text Link to item Cite

Characterization of a Drosophila U snRNP RNA-binding protein.

Journal Article Mol Biol Rep · 1990 Full text Link to item Cite

Downregulation of RNA polymerase III transcription of the hY3 gene in vitro.

Journal Article Mol Biol Rep · 1990 Full text Link to item Cite

Antigenicity of a recombinant Ro (SS-A) fusion protein.

Journal Article Arthritis Rheum · January 1990 The antigenicity of the 60-kd human Ro (SS-A) synthesized in vitro from its complementary DNA as a beta-galactosidase fusion protein (beta-gal-Ro) was evaluated by Western blotting. In this analysis, almost all the anti-Ro (SS-A)-positive sera that bound b ... Full text Link to item Cite

A specific 31-nucleotide domain of U1 RNA directly interacts with the 70K small nuclear ribonucleoprotein component.

Journal Article Mol Cell Biol · November 1989 We have defined the nucleotide sequence of a protein-binding domain within U1 RNA that specifically recognizes and binds both to a U1 small nuclear ribonucleoprotein component (the 70K protein) and to the previously defined RNA-binding domain of the 70K pr ... Full text Link to item Cite

Viral transcription is necessary and sufficient for vesicular stomatitis virus to inhibit maturation of small nuclear ribonucleoproteins.

Journal Article J Virol · October 1989 Infection of baby hamster kidney cells with vesicular stomatitis virus (VSV) results in the accumulation of immature U1 and U2 small nuclear ribonucleoproteins (snRNPs) that contain precursor U RNAs and at least some of the proteins specific for U1 and U2 ... Full text Link to item Cite

Inhibitory effects of vesicular stomatitis virus on cellular and influenza viral RNA metabolism and protein synthesis.

Journal Article Virology · September 1989 Infection with vesicular stomatitis virus (VSV) results in the rapid inhibition of cellular macromolecular synthesis, including transcription, translation, and maturation of the U1 and U2 snRNPs. Unlike infection with VSV, influenza virus infection did not ... Full text Link to item Cite

Epitope specificity of anti-La antibodies from patients with Sjögren's syndrome.

Journal Article J Autoimmun · August 1989 To investigate patterns of autoreactivity in Sjögren's syndrome, the epitope specificity of anti-La antibodies was determined using recombinant antigens bearing sequences of the amino, middle, and carboxyl portions of the La molecule. Sera from patients wi ... Full text Link to item Cite

Molecular structure of the La and Ro autoantigens and their use in autoimmune diagnostics.

Journal Article J Autoimmun · August 1989 Recombinant autoantigens of the La and Ro specificities have been produced and analyzed using immunological and genetic techniques. Human La cDNA and genomic clones were isolated that encode a protein of 46.7 kDa (408 amino acids). An active La gene consis ... Full text Link to item Cite

The U1 RNA-binding site of the U1 small nuclear ribonucleoprotein (snRNP)-associated A protein suggests a similarity with U2 snRNPs.

Journal Article Mol Cell Biol · July 1989 The site of interaction between human U1 RNA and one of its uniquely associated proteins, A, was examined with in vitro binding assays. The A protein bound directly to stem-loop II of U1 RNA in a region which exhibits sequence similarity to U2 RNA. The sim ... Full text Link to item Cite

A common RNA recognition motif identified within a defined U1 RNA binding domain of the 70K U1 snRNP protein.

Journal Article Cell · April 7, 1989 We have defined the RNA binding domain of the 70K protein component of the U1 small nuclear ribonucleoprotein to a region of 111 amino acids. This domain encompasses an octamer sequence that has been observed in other proteins associated with RNA, but has ... Full text Link to item Cite

A CARBOXY TERMINAL AUTOEPITOPE OF RO SSA

Conference CLINICAL RESEARCH · April 1, 1989 Link to item Cite

VARIATIONS IN SERUM ANTIBODY-LEVELS TO LA EPITOPES ON RECOMBINANT FUSION PROTEINS

Conference CLINICAL RESEARCH · April 1, 1989 Link to item Cite

Analysis of autoantibody binding to different regions of the human La antigen expressed in recombinant fusion proteins.

Journal Article J Immunol · December 15, 1988 To determine the specificity of autoantibodies for various antigenic sites on a self-protein molecule, sera from 19 patients with anti-La antibodies were tested for their reactivity with molecularly cloned La protein fragments. By quantitative ELISA, anti- ... Link to item Cite

Genomic structure and amino acid sequence domains of the human La autoantigen.

Journal Article J Biol Chem · December 5, 1988 La is an autoimmune RNA-binding protein of 47 kDa that plays a role in the transcription of RNA polymerase III. Both genomic and complementary DNAs were isolated that encompass the coding sequence of the human La molecule. The genomic clones encompass 11 e ... Link to item Cite

Molecular analysis of the 60-kDa human Ro ribonucleoprotein.

Journal Article Proc Natl Acad Sci U S A · December 1988 Ro, or Sjogren syndrome type A (SS-A), antigen is the most prevalent of the human systemic autoimmune specificities and exists as an inabundant ribonucleoprotein complex (RNP) composed of a 60,649-Da protein, as defined here by cDNA cloning, and the human ... Full text Link to item Cite

A sequence-specific conformational epitope on U1 RNA is recognized by a unique autoantibody.

Journal Article Proc Natl Acad Sci U S A · May 1988 An autoantibody from a patient with lupus-overlap syndrome was found to bind a specific region of U1 RNA. By using RNA sequence analysis, immunoprecipitation, and competition experiments with in vitro synthesized fragments of U1 RNA, a region of 40 nucleot ... Full text Link to item Cite

Quantitative immunoassay of anti-La antibodies using purified recombinant La antigen.

Journal Article Arthritis Rheum · April 1988 A purified recombinant La fusion protein was tested in an enzyme-linked immunosorbent assay to quantitate anti-La responses. This protein contained the immunodominant region of the La molecule fused to beta-galactosidase. In solid-phase assays, recombinant ... Full text Link to item Cite

HUMAN AUTOANTIBODIES RECOGNIZE MULTIPLE EPITOPES ON RECOMBINANT LA FUSION PROTEINS

Conference CLINICAL RESEARCH · April 1, 1988 Link to item Cite

LUPUS SERA FREQUENTLY RECOGNIZE CLONED U1 RNP-ASSOCIATED 70 K FUSION PROTEIN

Conference CLINICAL RESEARCH · April 1, 1988 Link to item Cite

A human autoimmune protein associated with U1 RNA contains a region of homology that is cross-reactive with retroviral p30gag antigen.

Journal Article Cell · October 23, 1987 cDNA encoding a 70 kd protein (70K) associated with U1 small nuclear ribonucleoprotein (snRNP) was cloned from a human brain-stem library using autoantibodies from patients with connective tissue disease. The cDNA-derived amino acid sequence contains 23 re ... Full text Link to item Cite