The 3’tsRNAs are aminoacylated: Implications for their biogenesis
Emerging evidence indicates that tRNA-derived small RNAs (tsRNAs) are involved in fine-tuning gene expression and become dysregulated in various cancers. We recently showed that the 22nt LeuCAG tsRNA from the 3' end of tRNA.sup.Leu is required for efficient translation of a ribosomal protein mR...
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| description | Emerging evidence indicates that tRNA-derived small RNAs (tsRNAs) are involved in fine-tuning gene expression and become dysregulated in various cancers. We recently showed that the 22nt LeuCAG tsRNA from the 3' end of tRNA.sup.Leu is required for efficient translation of a ribosomal protein mRNA and ribosome biogenesis. Inactivation of this 3'tsRNA induced apoptosis in rapidly dividing cells and suppressed the growth of a patient-derived orthotopic hepatocellular carcinoma in mice. The mechanism involved in the generation of the 3'tsRNAs remains elusive and it is unclear if the 3'-ends of 3'tsRNAs are aminoacylated. Here we report an enzymatic method utilizing exonuclease T to determine the 3'charging status of tRNAs and tsRNAs. Our results showed that the LeuCAG 3'tsRNA, and two other 3'tsRNAs are fully aminoacylated. When the leucyl-tRNA synthetase (LARS1) was inhibited, there was no change in the total tRNA.sup.Leu concentration but a reduction in both the charged tRNA.sup.Leu and LeuCAG 3'tsRNA, suggesting the 3'tsRNAs are fully charged and originated solely from the charged mature tRNA. Altering LARS1 expression or the expression of various tRNA.sup.Leu mutants were also shown to affect the generation of the LeuCAG 3'tsRNA further suggesting they are created in a highly regulated process. The fact that the 3'tsRNAs are aminoacylated and their production is regulated provides additional insights into their importance in post-transcriptional gene regulation that includes coordinating the production of the protein synthetic machinery. |
| doi_str_mv | 10.1371/journal.pgen.1009675 |
| format | Article |
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We recently showed that the 22nt LeuCAG tsRNA from the 3' end of tRNA.sup.Leu is required for efficient translation of a ribosomal protein mRNA and ribosome biogenesis. Inactivation of this 3'tsRNA induced apoptosis in rapidly dividing cells and suppressed the growth of a patient-derived orthotopic hepatocellular carcinoma in mice. The mechanism involved in the generation of the 3'tsRNAs remains elusive and it is unclear if the 3'-ends of 3'tsRNAs are aminoacylated. Here we report an enzymatic method utilizing exonuclease T to determine the 3'charging status of tRNAs and tsRNAs. Our results showed that the LeuCAG 3'tsRNA, and two other 3'tsRNAs are fully aminoacylated. When the leucyl-tRNA synthetase (LARS1) was inhibited, there was no change in the total tRNA.sup.Leu concentration but a reduction in both the charged tRNA.sup.Leu and LeuCAG 3'tsRNA, suggesting the 3'tsRNAs are fully charged and originated solely from the charged mature tRNA. Altering LARS1 expression or the expression of various tRNA.sup.Leu mutants were also shown to affect the generation of the LeuCAG 3'tsRNA further suggesting they are created in a highly regulated process. The fact that the 3'tsRNAs are aminoacylated and their production is regulated provides additional insights into their importance in post-transcriptional gene regulation that includes coordinating the production of the protein synthetic machinery.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1009675</identifier><identifier>PMID: 34324497</identifier><language>eng</language><publisher>San Francisco: Public Library of Science</publisher><subject>Apoptosis ; Biology and life sciences ; Biosynthesis ; Chemical properties ; E coli ; Exonuclease ; Gene expression ; Gene regulation ; Genetic aspects ; Genetic research ; Hepatocellular carcinoma ; Leucine-tRNA ligase ; Physiological aspects ; Post-transcription ; Protein synthesis ; Proteins ; Regulation ; Research and analysis methods ; Transfer RNA ; tRNA</subject><ispartof>PLoS genetics, 2021-07, Vol.17 (7), p.e1009675-e1009675</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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We recently showed that the 22nt LeuCAG tsRNA from the 3' end of tRNA.sup.Leu is required for efficient translation of a ribosomal protein mRNA and ribosome biogenesis. Inactivation of this 3'tsRNA induced apoptosis in rapidly dividing cells and suppressed the growth of a patient-derived orthotopic hepatocellular carcinoma in mice. The mechanism involved in the generation of the 3'tsRNAs remains elusive and it is unclear if the 3'-ends of 3'tsRNAs are aminoacylated. Here we report an enzymatic method utilizing exonuclease T to determine the 3'charging status of tRNAs and tsRNAs. Our results showed that the LeuCAG 3'tsRNA, and two other 3'tsRNAs are fully aminoacylated. When the leucyl-tRNA synthetase (LARS1) was inhibited, there was no change in the total tRNA.sup.Leu concentration but a reduction in both the charged tRNA.sup.Leu and LeuCAG 3'tsRNA, suggesting the 3'tsRNAs are fully charged and originated solely from the charged mature tRNA. Altering LARS1 expression or the expression of various tRNA.sup.Leu mutants were also shown to affect the generation of the LeuCAG 3'tsRNA further suggesting they are created in a highly regulated process. 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We recently showed that the 22nt LeuCAG tsRNA from the 3' end of tRNA.sup.Leu is required for efficient translation of a ribosomal protein mRNA and ribosome biogenesis. Inactivation of this 3'tsRNA induced apoptosis in rapidly dividing cells and suppressed the growth of a patient-derived orthotopic hepatocellular carcinoma in mice. The mechanism involved in the generation of the 3'tsRNAs remains elusive and it is unclear if the 3'-ends of 3'tsRNAs are aminoacylated. Here we report an enzymatic method utilizing exonuclease T to determine the 3'charging status of tRNAs and tsRNAs. Our results showed that the LeuCAG 3'tsRNA, and two other 3'tsRNAs are fully aminoacylated. When the leucyl-tRNA synthetase (LARS1) was inhibited, there was no change in the total tRNA.sup.Leu concentration but a reduction in both the charged tRNA.sup.Leu and LeuCAG 3'tsRNA, suggesting the 3'tsRNAs are fully charged and originated solely from the charged mature tRNA. Altering LARS1 expression or the expression of various tRNA.sup.Leu mutants were also shown to affect the generation of the LeuCAG 3'tsRNA further suggesting they are created in a highly regulated process. The fact that the 3'tsRNAs are aminoacylated and their production is regulated provides additional insights into their importance in post-transcriptional gene regulation that includes coordinating the production of the protein synthetic machinery.</abstract><cop>San Francisco</cop><pub>Public Library of Science</pub><pmid>34324497</pmid><doi>10.1371/journal.pgen.1009675</doi><orcidid>https://orcid.org/0000-0002-2799-2615</orcidid><orcidid>https://orcid.org/0000-0003-0143-8824</orcidid><orcidid>https://orcid.org/0000-0002-9701-8228</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Apoptosis Biology and life sciences Biosynthesis Chemical properties E coli Exonuclease Gene expression Gene regulation Genetic aspects Genetic research Hepatocellular carcinoma Leucine-tRNA ligase Physiological aspects Post-transcription Protein synthesis Proteins Regulation Research and analysis methods Transfer RNA tRNA |
| title | The 3’tsRNAs are aminoacylated: Implications for their biogenesis |
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