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
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
