TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35444240.
- Also identified by DOI 10.1038/s41467-022-29790-8 and PMC identifier 9021294.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
RNA modifications are important regulatory elements of RNA functions. However, most genome-wide mapping of RNA modifications has focused on messenger RNAs and transfer RNAs, but such datasets have been lacking for small RNAs. Here we mapped N<sup>1</sup>-methyladenosine (m<sup>1</sup>A) in the cellular small RNA space. Benchmarked with synthetic m<sup>1</sup>A RNAs, our workflow identified specific groups of m<sup>1</sup>A-containing small RNAs, which are otherwise disproportionally under-represented. In particular, 22-nucleotides long 3' tRNA-fragments are highly enriched for TRMT6/61A-dependent m<sup>1</sup>A located within the seed region. TRMT6/61A-dependent m<sup>1</sup>A negatively affects gene silencing by tRF-3s. In urothelial carcinoma of the bladder, where TRMT6/61A is over-expressed, higher m<sup>1</sup>A modification on tRFs is detected, correlated with a dysregulation of tRF targetome. Lastly, TRMT6/61A regulates tRF-3 targets involved in unfolded protein response. Together, our results reveal a mechanism of regulating gene expression via base modification of small RNA.
Medical subject headings
- Carcinoma, Transitional Cell
- Urinary Bladder Neoplasms