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

Publication ,  Journal Article
Morris, AR; Mukherjee, N; Keene, JD
Published in: 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 and analyze mRNAs associated with ribonucleoproteins containing an endogenous human PUF protein, Pum1. Pum1-associated mRNAs were highly enriched for genes encoding proteins that function in transcriptional regulation and cell cycle/proliferation, results consistent with the posttranscriptional RNA regulon model and the proposed ancestral functions of PUF proteins in stem cell biology. Analysis of 3' untranslated region sequences of Pum1-associated mRNAs revealed a core Pum1 consensus sequence, UGUAHAUA. Pum1 knockdown demonstrated that Pum1 enhances decay of associated mRNAs, and relocalization of Pum1 to stress granules suggested that Pum1 functions in repression of translation. This study is the first in vivo genome-wide mRNA target identification of a mammalian PUF protein and provides direct evidence that human PUF proteins regulate stability of associated mRNAs. Comparison of Pum1-associated mRNAs to mRNA targets of PUF proteins from Saccharomyces cerevisiae and Drosophila melanogaster demonstrates how a well-conserved RNA-binding domain and cognate binding sequence have been evolutionarily rewired to regulate the collective expression of different sets of functionally related genes.

Duke Scholars

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

June 2008

Volume

28

Issue

12

Start / End Page

4093 / 4103

Location

United States

Related Subject Headings

  • Species Specificity
  • Saccharomyces cerevisiae
  • Ribosomes
  • RNA-Binding Proteins
  • RNA, Messenger
  • Protein Biosynthesis
  • Oxidative Stress
  • Oligonucleotide Array Sequence Analysis
  • Models, Biological
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
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Morris, A. R., Mukherjee, N., & Keene, J. D. (2008). Ribonomic analysis of human Pum1 reveals cis-trans conservation across species despite evolution of diverse mRNA target sets. Mol Cell Biol, 28(12), 4093–4103. https://doi.org/10.1128/MCB.00155-08
Morris, Adam R., Neelanjan Mukherjee, and Jack D. Keene. “Ribonomic analysis of human Pum1 reveals cis-trans conservation across species despite evolution of diverse mRNA target sets.Mol Cell Biol 28, no. 12 (June 2008): 4093–4103. https://doi.org/10.1128/MCB.00155-08.
Morris, Adam R., et al. “Ribonomic analysis of human Pum1 reveals cis-trans conservation across species despite evolution of diverse mRNA target sets.Mol Cell Biol, vol. 28, no. 12, June 2008, pp. 4093–103. Pubmed, doi:10.1128/MCB.00155-08.

Published In

Mol Cell Biol

DOI

EISSN

1098-5549

Publication Date

June 2008

Volume

28

Issue

12

Start / End Page

4093 / 4103

Location

United States

Related Subject Headings

  • Species Specificity
  • Saccharomyces cerevisiae
  • Ribosomes
  • RNA-Binding Proteins
  • RNA, Messenger
  • Protein Biosynthesis
  • Oxidative Stress
  • Oligonucleotide Array Sequence Analysis
  • Models, Biological
  • Humans