Journal
NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-29790-8
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Funding
- NCI Cancer Center Support Grant [5P30CA044579]
- NIH F30 Fellowship [CA254134]
- NIH [AR067712, K99 CA259526]
- Vestre Viken Hospital Trust [25C003]
- Norwegian Cancer Society [216115]
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This study reveals the presence of N-1-methyladenosine modification in small RNAs, which acts as a regulatory element in gene expression. The higher level of m(1)A modification in bladder cancer is associated with dysregulation of genes involved in unfolded protein response.
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-1-methyladenosine (m(1)A) in the cellular small RNA space. Benchmarked with synthetic m(1)A RNAs, our workflow identified specific groups of m(1)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(1)A located within the seed region. TRMT6/61A-dependent m(1)A negatively affects gene silencing by tRF-3s. In urothelial carcinoma of the bladder, where TRMT6/61A is over-expressed, higher m(1)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. RNA modifications are important regulators of RNA biology. Here we report N-1-methyladenosine (m(1)A) enrichment on 22-nucleotide tRNA fragments and its effect on gene-silencing. Higher level of m(1)A in bladder cancer is accompanied by gene dysregulation in unfolded protein response.
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