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 N1-methyladenosine (m1A) in the cellular small RNA space. Benchmarked with synthetic m1A RNAs, our workflow identified specific groups of m1A-containing small RNAs, which are otherwise disproportionally under-represented. In particular, 22-nucleotides long 3′ tRNA-fragments are highly enriched for TRMT6/61A-dependent m1A located within the seed region. TRMT6/61A-dependent m1A negatively affects gene silencing by tRF-3s. In urothelial carcinoma of the bladder, where TRMT6/61A is over-expressed, higher m1A 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.
【초록키워드】 RNA modification, Gene Expression, RNAs, RNA, unfolded protein response, target, dataset, gene silencing, group, mechanism, cellular, regulate, dysregulation, Small RNAs, Messenger RNA, transfer, functions, Modification, bladder, Affect, involved, correlated, mapped, over-expressed, regulatory element, N1-methyladenosine, 【제목키워드】 unfolded protein response, Methylation, Bladder cancer, regulate,