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Updated: May 21, 2025

An In Vitro Assay to Detect tRNA-Isopentenyl Transferase Activity
Published on: October 8, 2018
TRIM21 modulates stability of pro-survival non-coding RNA vtRNA1-1 in human hepatocellular carcinoma cells
EunBin Kong1, Norbert Polacek1
1Department for Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland.
Abstract:
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.
Insights
New research identifies TRIM21 and TRIM25 proteins that stabilize vault RNA 1-1 (vtRNA1-1) in liver cancer cells. This discovery offers potential new strategies for developing anticancer therapies.
Area of Science:
- Molecular Biology
- Oncology
- RNA Biology
Background:
- Short non-coding vault RNAs, including vtRNA1-1, play diverse pro-survival roles in cancer cells.
- vtRNA1-1 influences proliferation, apoptosis, autophagy, and drug resistance in human cancers.
- The protein interactions and regulatory mechanisms controlling vtRNA1-1 levels were previously unknown.
Purpose of the Study:
- To identify protein interaction partners that regulate vtRNA1-1 stability.
- To elucidate the mechanisms controlling vtRNA1-1 levels in hepatocellular carcinoma (HCC) cells.
- To explore the role of methylation in vtRNA1-1 stability.
Main Methods:
- Investigated the interaction of vtRNA1-1 with TRIM21 and TRIM25 in HCC cells.
- Utilized in vivo and in vitro experiments to assess vtRNA1-1 stability upon depletion of TRIM proteins.
- Identified the specific vtRNA1-1 sequence involved in stability regulation and analyzed NSUN2-mediated methylation at C69.
Main Results:
- TRIM21 and TRIM25 were identified as novel interacting proteins that stabilize vtRNA1-1 in HCC cells.
- Depletion of TRIM21 or TRIM25 significantly reduced vtRNA1-1 stability.
- NSUN2-mediated methylation at C69 of vtRNA1-1 was found to be critical for its stability, regulated by TRIM proteins.
Conclusions:
- TRIM proteins (TRIM21 and TRIM25) govern vtRNA1-1 stability in HCC cells, dependent on its methylation status.
- Understanding vtRNA1-1 regulation by TRIM proteins and its methylation provides insight into cancer cell survival mechanisms.
- These findings may inform the development of novel therapeutic strategies targeting vtRNA1-1 in hepatocellular carcinoma.
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