4.8 Article

Human Argonaute2 and Argonaute3 are catalytically activated by different lengths of guide RNA

出版社

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2015026117

关键词

RNAi; Argonaute; noncoding RNA; enzyme

资金

  1. Pelotonia Fellowship
  2. Center for RNA Fellowship
  3. NIH [R01GM124320, R01GM138997]
  4. Office of the Director, NIH [S10OD023582]

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RNA interfering is a eukaryote-specific gene silencing by 20-23 nucleotide (nt) microRNAs and small interfering RNAs that recruit Argonaute proteins to complementary RNAs for degradation. In humans, Argonaute2 (AGO2) has been known as the only slicer while Argonaute3 (AGO3) barely cleaves RNAs. Therefore, the intrinsic slicing activity of AGO3 remains controversial and a longstanding question. Here, we report 14-nt 3 ' end-shortened variants of let-7a, miR-27a, and specific miR-17-92 families that make AGO3 an extremely competent slicer, increasing target cleavage up to-82-fold in some instances. These RNAs, named cleavageinducing tiny guide RNAs (cityRNAs), conversely lower the activity of AGO2, demonstrating that AGO2 and AGO3 have different optimum guide lengths for target cleavage. Our study sheds light on the role of tiny guide RNAs.

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