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Discovery of the major 15–30 nt mammalian small RNAs, their biogenesis and function

Author

Listed:
  • Hejin Lai

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Ning Feng

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Qiwei Zhai

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences
    ShanghaiTech University)

Abstract

Small RNAs (sRNAs) within 15-30 nt such as miRNA, tsRNA, srRNA with 3’-OH have been identified. However, whether these sRNAs are the major 15-30 nt sRNAs is still unknown. Here we show about 90% mammalian sRNAs within 15-30 nt end with 2’,3’-cyclic phosphate (3’-cP). TANT-seq was developed to simultaneously profile sRNAs with 3’-cP (sRNA-cPs) and sRNA-OHs, and huge amount of sRNA-cPs were detected. Surprisingly, sRNA-cPs and sRNA-OHs usually have distinct sequences. The data from TANT-seq were validated by a novel method termed TE-qPCR, and Northern blot. Furthermore, we found that Angiogenin and RNase 4 contribute to the biogenesis of sRNA-cPs. Moreover, much more sRNA-cPs than sRNA-OHs bind to Ago2, and can regulate gene expression. Particularly, snR-2-cP regulates Bcl2 by targeting to its 3’UTR dependent on Ago2, and subsequently regulates apoptosis. In addition, sRNA-cPs can guide the cleavage of target RNAs in Ago2 complex as miRNAs without the requirement of 3’-cP. Our discovery greatly expands the repertoire of mammalian sRNAs, and provides strategies and powerful tools towards further investigation of sRNA-cPs.

Suggested Citation

  • Hejin Lai & Ning Feng & Qiwei Zhai, 2023. "Discovery of the major 15–30 nt mammalian small RNAs, their biogenesis and function," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41554-6
    DOI: 10.1038/s41467-023-41554-6
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    1. Hak Kyun Kim & Gabriele Fuchs & Shengchun Wang & Wei Wei & Yue Zhang & Hyesuk Park & Biswajoy Roy-Chaudhuri & Pan Li & Jianpeng Xu & Kirk Chu & Feijie Zhang & Mei-Sze Chua & Samuel So & Qiangfeng Clif, 2017. "A transfer-RNA-derived small RNA regulates ribosome biogenesis," Nature, Nature, vol. 552(7683), pages 57-62, December.
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    3. Alexei Aravin & Dimos Gaidatzis & Sébastien Pfeffer & Mariana Lagos-Quintana & Pablo Landgraf & Nicola Iovino & Patricia Morris & Michael J. Brownstein & Satomi Kuramochi-Miyagawa & Toru Nakano & Minc, 2006. "A novel class of small RNAs bind to MILI protein in mouse testes," Nature, Nature, vol. 442(7099), pages 203-207, July.
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