TRIM21 modulates stability of pro-survival non-coding RNA vtRNA1-1 in human hepatocellular carcinoma cells.
Recent studies expanded our knowledge of diverse pro-survival functions of short non-coding vault RNAs. One of the human vault RNA paralogs, vtRNA1-1, modulates several intracellular processes, including proliferation, apoptosis, autophagy, and drug resistance in various types of human cancer cells....
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| Format: | Article |
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Public Library of Science (PLoS)
2025-03-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011614 |
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| author | EunBin Kong Norbert Polacek |
| author_facet | EunBin Kong Norbert Polacek |
| author_sort | EunBin Kong |
| collection | DOAJ |
| description | Recent studies expanded our knowledge of diverse pro-survival functions of short non-coding vault RNAs. One of the human vault RNA paralogs, vtRNA1-1, modulates several intracellular processes, including proliferation, apoptosis, autophagy, and drug resistance in various types of human cancer cells. However, protein interaction partners and mechanisms by which vtRNA1-1 levels are controlled within the cells remained elusive. Here, we describe a regulatory process for vtRNA1-1 stabilization mediated by the newly identified interacting proteins, TRIM21 and TRIM25, in human hepatocellular carcinoma (HCC) cells. Depleting TRIM21 or TRIM25 reduced the stability of vtRNA1-1 both in vivo and in vitro. We also identified the responsible sequence of vtRNA1-1 for the stability regulation by TRIM21 and TRIM25 and revealed another critical factor for vtRNA1-1 stability, an NSUN2-mediated methylation at C69 of vtRNA1-1. Consequently, our findings demonstrated that the TRIM proteins govern the stability of vtRNA1-1 depending on its methylation status in HCC cells. Since vtRNA1-1 is crucial for pro-survival characteristics in HCC cells, insight into vtRNA1-1 protein binding partners and the regulation of its stability can impact the development of new anticancer strategies. |
| format | Article |
| id | doaj-art-76ee752fe3db4b93900dd5a3f03334cd |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS Genetics |
| spelling | doaj-art-76ee752fe3db4b93900dd5a3f03334cd2025-08-20T01:55:30ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-03-01213e101161410.1371/journal.pgen.1011614TRIM21 modulates stability of pro-survival non-coding RNA vtRNA1-1 in human hepatocellular carcinoma cells.EunBin KongNorbert PolacekRecent studies expanded our knowledge of diverse pro-survival functions of short non-coding vault RNAs. One of the human vault RNA paralogs, vtRNA1-1, modulates several intracellular processes, including proliferation, apoptosis, autophagy, and drug resistance in various types of human cancer cells. However, protein interaction partners and mechanisms by which vtRNA1-1 levels are controlled within the cells remained elusive. Here, we describe a regulatory process for vtRNA1-1 stabilization mediated by the newly identified interacting proteins, TRIM21 and TRIM25, in human hepatocellular carcinoma (HCC) cells. Depleting TRIM21 or TRIM25 reduced the stability of vtRNA1-1 both in vivo and in vitro. We also identified the responsible sequence of vtRNA1-1 for the stability regulation by TRIM21 and TRIM25 and revealed another critical factor for vtRNA1-1 stability, an NSUN2-mediated methylation at C69 of vtRNA1-1. Consequently, our findings demonstrated that the TRIM proteins govern the stability of vtRNA1-1 depending on its methylation status in HCC cells. Since vtRNA1-1 is crucial for pro-survival characteristics in HCC cells, insight into vtRNA1-1 protein binding partners and the regulation of its stability can impact the development of new anticancer strategies.https://doi.org/10.1371/journal.pgen.1011614 |
| spellingShingle | EunBin Kong Norbert Polacek TRIM21 modulates stability of pro-survival non-coding RNA vtRNA1-1 in human hepatocellular carcinoma cells. PLoS Genetics |
| title | TRIM21 modulates stability of pro-survival non-coding RNA vtRNA1-1 in human hepatocellular carcinoma cells. |
| title_full | TRIM21 modulates stability of pro-survival non-coding RNA vtRNA1-1 in human hepatocellular carcinoma cells. |
| title_fullStr | TRIM21 modulates stability of pro-survival non-coding RNA vtRNA1-1 in human hepatocellular carcinoma cells. |
| title_full_unstemmed | TRIM21 modulates stability of pro-survival non-coding RNA vtRNA1-1 in human hepatocellular carcinoma cells. |
| title_short | TRIM21 modulates stability of pro-survival non-coding RNA vtRNA1-1 in human hepatocellular carcinoma cells. |
| title_sort | trim21 modulates stability of pro survival non coding rna vtrna1 1 in human hepatocellular carcinoma cells |
| url | https://doi.org/10.1371/journal.pgen.1011614 |
| work_keys_str_mv | AT eunbinkong trim21modulatesstabilityofprosurvivalnoncodingrnavtrna11inhumanhepatocellularcarcinomacells AT norbertpolacek trim21modulatesstabilityofprosurvivalnoncodingrnavtrna11inhumanhepatocellularcarcinomacells |