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

doi:10.1016/j.celrep.2019.11.062

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

Cell Rep. 2019 Dec 17;29(12):3816-3824.e4. doi: 10.1016/j.celrep.2019.11.062.

Authors

Hak Kyun Kim¹, Jianpeng Xu², Kirk Chu², Hyesuk Park², Hagoon Jang², Pan Li³, Paul N Valdmanis⁴, Qiangfeng Cliff Zhang³, Mark A Kay⁵

Affiliations

¹ 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.
² Department of Pediatrics, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA.
³ 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.
⁴ Division of Medical Genetics, Department of Medicine, University of Washington, Seattle, WA 98195, USA.
⁵ Department of Pediatrics, Stanford University, Stanford, CA 94305, USA; Department of Genetics, Stanford University, Stanford, CA 94305, USA. Electronic address: markay@stanford.edu.

Abstract

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.

Keywords: ribosomal proteins; tRF; tRNA fragments; tRNA-derived small RNAs; translation; tsRNA.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Humans
Leucine / genetics*
Leucine / metabolism
Mice
Phylogeny
Protein Biosynthesis*
Protein Processing, Post-Translational*
RNA, Messenger / genetics*
RNA, Messenger / metabolism
RNA, Small Untranslated / genetics*
RNA, Small Untranslated / metabolism
RNA, Transfer / genetics*
RNA, Transfer / metabolism
Ribosomal Proteins / genetics
Ribosomal Proteins / metabolism*

Substances

RNA, Messenger
RNA, Small Untranslated
RPS28 protein, human
Ribosomal Proteins
RNA, Transfer
Leucine

Abstract

Publication types

MeSH terms

Substances

Grants and funding