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TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer

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  • Zhangli Su

    (University of Alabama
    University of Virginia)

  • Ida Monshaugen

    (Oslo University Hospital Rikshospitalet
    University of Oslo
    Baerum Hospital Vestre Viken Hospital Trust)

  • Briana Wilson

    (University of Virginia)

  • Fengbin Wang

    (University of Virginia)

  • Arne Klungland

    (Oslo University Hospital Rikshospitalet
    University of Oslo)

  • Rune Ougland

    (Oslo University Hospital Rikshospitalet
    Baerum Hospital Vestre Viken Hospital Trust)

  • Anindya Dutta

    (University of Alabama
    University of Virginia)

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.

Suggested Citation

  • Zhangli Su & Ida Monshaugen & Briana Wilson & Fengbin Wang & Arne Klungland & Rune Ougland & Anindya Dutta, 2022. "TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29790-8
    DOI: 10.1038/s41467-022-29790-8
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