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

Hejin Lai, Ning Feng and Qiwei Zhai ()
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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

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41554-6

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