The human non-coding RNA vtRNA1-1 modulates several processes which are important for cancer cells. However, how the levels of vtRNA1-1 are regulated in cells as so far been unknown. The Polacek lab identified the proteins TRIM21 and TRIM25 as interactors and stabilizers of vtRNA1-1. Furthermore, they could show that methylation of a single nucleotide in vtRNA1-1 affects its stability as well. Their article "" has been published in PLoS Genetics.
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.
Read the Publication in PLoS Genetics (Open Access)
Abstract, figure and title from Kong and Polacek (2025) PLoS Genet published under a CC BY 4.0 license.