Talk abstracts
Talk on Friday 01:00-01:15pm submitted by GeunYoung Sim
Human Argonaute2 and Argonaute3 are catalytically activated by different lengths of guide RNA
GeunYoung Sim (Molecular, Cellular and Developmental Biology and Center for RNA Biology, The Ohio State University), Mi Seul Park (Department of Chemistry and Biochemistry and Center for RNA Biology, The Ohio State University), Audrey C. Kehling (Department of Chemistry and Biochemistry, The Ohio State University), Kotaro Nakanishi (Department of Chemistry and Biochemistry, Molecular, Cellular and Developmental Biology and Center for RNA Biology, The Ohio State University)
Abstract:
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, increasing target cleavage up to ~ 82-fold in some instances. 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.
References:
1. Posted on bioRxiv, doi: https://doi.org/10.1101/2020.07.16.207720
2. Park MS, Araya-Secchi R, Brackbill JA, et al. Multidomain Convergence of Argonaute during RISC Assembly Correlates with the Formation of Internal Water Clusters. Mol Cell. 2019;75(4):725-740.e6. doi:10.1016/j.molcel.2019.06.011
Keywords: Argonaute, small RNAs, RNA cleavage