A tRNA-Derived Small RNA Regulates Ribosomal Protein S28 Protein Levels after Translation Initiation in Humans and Mice

Hak Kyun Kim; Jianpeng Xu; Kirk Chu; Hyesuk Park; Hagoon Jang; Pan Li; Paul N. Valdmanis; Qiangfeng Cliff Zhang; Mark A. Kay

Cell Reports (Dec 2019)

A tRNA-Derived Small RNA Regulates Ribosomal Protein S28 Protein Levels after Translation Initiation in Humans and Mice

Hak Kyun Kim,
Jianpeng Xu,
Kirk Chu,
Hyesuk Park,
Hagoon Jang,
Pan Li,
Paul N. Valdmanis,
Qiangfeng Cliff Zhang,
Mark A. Kay

Affiliations

Hak Kyun Kim: Department of Pediatrics, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Department of Life Science, Chung-Ang University, Seoul 156-756, Republic of Korea
Jianpeng Xu: Department of Pediatrics, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA
Kirk Chu: Department of Pediatrics, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA
Hyesuk Park: Department of Pediatrics, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA
Hagoon Jang: Department of Pediatrics, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA
Pan Li: MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology, Center for Synthetic and Systems Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
Paul N. Valdmanis: Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA
Qiangfeng Cliff Zhang: MOE Key Laboratory of Bioinformatics, Beijing Advanced Innovation Center for Structural Biology, Center for Synthetic and Systems Biology, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
Mark A. Kay: Department of Pediatrics, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA; Corresponding author

Journal volume & issue: Vol. 29, no. 12
pp. 3816 – 3824.e4

Abstract

Read online

Summary: tRNA-derived small RNAs (tsRNAs) have been implicated in many cellular processes, yet the detailed mechanisms are not well defined. We previously found that the 3′ end of Leu-CAG tRNA-derived small RNA (LeuCAG3′tsRNA) regulates ribosome biogenesis in humans by maintaining ribosomal protein S28 (RPS28) levels. The tsRNA binds to coding (CDS) and non-coding 3′ UTR sequence in the RPS28 mRNA, altering its secondary structure and enhancing its translation. Here we report that the functional 3′ UTR target site is present in primates while the CDS target site is present in many vertebrates. We establish that this tsRNA also regulates mouse Rps28 translation by interacting with the CDS target site. We further establish that the change in mRNA translation occurred at a post-initiation step in both species. Overall, our results suggest that LeuCAG3′tsRNA might maintain ribosome biogenesis through a conserved gene regulatory mechanism in vertebrates. : Kim et al. determined that the LeuCAG3′tsRNA target site in the RPS28 coding sequence (CDS) is conserved in vertebrates and established that the tsRNA regulation of RPS28 mRNA translation is conserved between humans and mice. Their results suggest that the tsRNA-regulated mRNA translation might be a conserved process. Keywords: tRNA-derived small RNAs, tsRNA, tRF, tRNA fragments, ribosomal proteins, translation

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal