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.

Plos Genetics
|March 17, 2025
PubMed

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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