RT Journal Article
SR Electronic
T1 Human Argonaute2 and Argonaute3 are catalytically activated by different lengths of guide RNA
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.16.207720
DO 10.1101/2020.07.16.207720
A1 Park, Mi Seul
A1 Sim, GeunYoung
A1 Kehling, Audrey C.
A1 Nakanishi, Kotaro
YR 2020
UL http://biorxiv.org/content/early/2020/07/17/2020.07.16.207720.abstract
AB 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 long-standing 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 by an ∼ 82-fold increase in target cleavage. These RNAs, named cleavage-inducing 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.Competing Interest StatementThe authors have declared no competing interest.