PT  - JOURNAL ARTICLE
AU  - Mi Seul Park
AU  - GeunYoung Sim
AU  - Audrey C. Kehling
AU  - Kotaro Nakanishi
TI  - Human Argonaute2 and Argonaute3 are catalytically activated by different lengths of guide RNA
AID  - 10.1101/2020.07.16.207720
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.16.207720
4099  - http://biorxiv.org/content/early/2020/07/17/2020.07.16.207720.short
4100  - http://biorxiv.org/content/early/2020/07/17/2020.07.16.207720.full
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.