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Abstract 378: Physiologic Role of Rpl13a SnoRNAs in Cell Size Regulation

Publication ,  Conference
Ho, HTT; Holley, CL
Published in: Circulation Research
July 31, 2020

Box C/D small nucleolar RNAs (snoRNA) are a multifunctional family of ncRNAs that play a critical role in guiding 2'- -methylation (Nm) of ribosomal RNA (rRNA). My work has recently revealed that box C/D snoRNAs can also direct methylation of messenger RNA (mRNA), and that this methylation can regulate mRNA translation in the heart. In studies of genetically-engineered mice lacking four box C/D snoRNAs, I have observed that the knockout animals have relatively small hearts compared to wild-type. The objective of my current study is to define the specific mechanisms by which box C/D snoRNAs regulate heart size. I investigated the hearts of genetically-engineered mice lacking four box C/D snoRNAs from the locus (snoRNAs and ). I also used antisense oligonucleotides to knock down these snoRNAs in H9c2 rat cardiomyoblasts. Changes in gene and protein expression were assessed by qPCR and immunoblot. Relative Nm modification of mRNA was determined by reverse transcription at low dNTP concentrations, followed by real-time PCR (RTL-P). Germline knockout of the four box C/D snoRNAs ( and ) in adolescent mice produces developmentally smaller hearts. In H9c2 rat cardiomyoblasts, knockdown of snoRNAs by antisense oligonucleotides significantly reduces H9c2 cell size. These concordant effects on organ and cell size suggest that the snoRNAs might be regulating critical pathways that determine cell growth. Using a candidate gene approach, I found that mRNA and protein expression is significantly reduced in hearts from snoRNA knockout mice. Preliminary results using the RTL-P method suggest that is subject to snoRNA-guided Nm modification, which is decreased in snoRNA knockout mouse hearts. These results suggest that snoRNAs regulate cardiomyocyte growth, at least in part, by guiding Nm modification of mRNA.

Duke Scholars

Published In

Circulation Research

DOI

EISSN

1524-4571

ISSN

0009-7330

Publication Date

July 31, 2020

Volume

127

Issue

Suppl_1

Publisher

Ovid Technologies (Wolters Kluwer Health)

Related Subject Headings

  • Cardiovascular System & Hematology
  • 3202 Clinical sciences
  • 3201 Cardiovascular medicine and haematology
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

APA
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ICMJE
MLA
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Ho, H. T. T., & Holley, C. L. (2020). Abstract 378: Physiologic Role of Rpl13a SnoRNAs in Cell Size Regulation. In Circulation Research (Vol. 127). Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1161/res.127.suppl_1.378
Ho, Hsiang Ting T., and Christopher L. Holley. “Abstract 378: Physiologic Role of Rpl13a SnoRNAs in Cell Size Regulation.” In Circulation Research, Vol. 127. Ovid Technologies (Wolters Kluwer Health), 2020. https://doi.org/10.1161/res.127.suppl_1.378.
Ho HTT, Holley CL. Abstract 378: Physiologic Role of Rpl13a SnoRNAs in Cell Size Regulation. In: Circulation Research. Ovid Technologies (Wolters Kluwer Health); 2020.
Ho, Hsiang Ting T., and Christopher L. Holley. “Abstract 378: Physiologic Role of Rpl13a SnoRNAs in Cell Size Regulation.” Circulation Research, vol. 127, no. Suppl_1, Ovid Technologies (Wolters Kluwer Health), 2020. Crossref, doi:10.1161/res.127.suppl_1.378.
Ho HTT, Holley CL. Abstract 378: Physiologic Role of Rpl13a SnoRNAs in Cell Size Regulation. Circulation Research. Ovid Technologies (Wolters Kluwer Health); 2020.

Published In

Circulation Research

DOI

EISSN

1524-4571

ISSN

0009-7330

Publication Date

July 31, 2020

Volume

127

Issue

Suppl_1

Publisher

Ovid Technologies (Wolters Kluwer Health)

Related Subject Headings

  • Cardiovascular System & Hematology
  • 3202 Clinical sciences
  • 3201 Cardiovascular medicine and haematology
  • 1103 Clinical Sciences
  • 1102 Cardiorespiratory Medicine and Haematology