Poster abstracts
Poster number 45 submitted by GeunYoung Sim
Manganese-dependent microRNA trimming by 3′→5′ exonucleases generates 14-nucleotide or shorter tiny RNAs.
GeunYoung Sim (The Ohio State University, Molecular, Cellular and Developmental Biology, Columbus, OH), Audrey Kehling, Jackson Secor, Huaqun Zhang (The Ohio State University, Center for RNA Biology, Columbus, OH 43210, USA), Nipun Malhotra, Divyaa Bhagdikar, Ekram A. El-Wahaband (The Ohio State University, Center for RNA Biology, Columbus, OH 43210, USA), Mi Seul Park (The Ohio State University, Chemistry and Biochemistry, Columbus, OH), Cameron Divoky (The Ohio State University, Ohio State Biochemistry Program, Columbus, OH 43210, USA), Kotaro Nakanishi (The Ohio State University, Molecular, Cellular and Developmental Biology, Chemistry and Biochemistry, Ohio State Biochemistry Program, Columbus, OH 43210, USA)
Abstract:
MicroRNAs (miRNAs) are about 22-nucleotide (nt) non-coding RNAs forming the effector complexes with Argonaute (AGO) proteins to repress gene expression. Although tiny RNAs (tyRNAs) shorter than 19 nt have been found to bind to plant and vertebrate AGOs, their biogenesis remains a long-standing question. Here, our in vivo and in vitro studies show several 3′→5′ exonucleases, such as interferon-stimulated gene 20 kDa (ISG20), three prime repair exonuclease 1 (TREX1), and ERI1 (enhanced RNAi, also known as 3′hExo), capable of trimming AGO-associated full-length miRNAs to 14-nt or shorter tyRNAs. Their guide trimming occurs in a manganese-dependent manner but independently of the guide sequence and the loaded four human AGO paralogs. We also show that ISG20-mediated guide trimming makes Argonaute3 (AGO3) a slicer. Given the high Mn2+ concentrations in stressed cells, virus-infected cells, and neurodegeneration, our study sheds light on the roles of the Mn2+-dependent exonucleases in remodeling gene silencing.
References:
G. Sim et al., Manganese-dependent microRNA trimming by 3′→5′ exonucleases generates 14-nucleotide or shorter tiny RNAs. Proc Natl Acad Sci U S A 119(51):e2214335119 (2022).
V. Ambros et al., A uniform system for microRNA annotation. RNA 9, 277-279 (2003).
K. Nakanishi, Anatomy of RISC: how do small RNAs and chaperones activate Argonaute proteins? Wiley Interdiscip Rev RNA 7, 637-660 (2016).
K. Nakanishi, Are Argonaute-Associated Tiny RNAs Junk, Inferior miRNAs, or a New Type of Functional RNAs? Front Mol Biosci 8, 795356 (2021).
A. M. Stankiewicz et al., The Effect of Acute and Chronic Social Stress on the Hippocampal Transcriptome in Mice. PLoS One 10, e0142195 (2015).
M. S. Park et al., Human Argonaute2 and Argonaute3 are catalytically activated by different lengths of guide RNA. Proc Natl Acad Sci U S A 117, 28576-28578 (2020).
Keywords: RNAi, non-coding RNAs, exonucleases