Caenorhabditis elegans ALG-1 antimorphic mutations uncover functions for Argonaute in microRNA guide strand selection and passenger strand disposal

Proceedings of the National Academy of Sciences of the United States of America
Anna Y ZinovyevaVictor Ambros

Abstract

MicroRNAs are regulators of gene expression whose functions are critical for normal development and physiology. We have previously characterized mutations in a Caenorhabditis elegans microRNA-specific Argonaute ALG-1 (Argonaute-like gene) that are antimorphic [alg-1(anti)]. alg-1(anti) mutants have dramatically stronger microRNA-related phenotypes than animals with a complete loss of ALG-1. ALG-1(anti) miRISC (microRNA induced silencing complex) fails to undergo a functional transition from microRNA processing to target repression. To better understand this transition, we characterized the small RNA and protein populations associated with ALG-1(anti) complexes in vivo. We extensively characterized proteins associated with wild-type and mutant ALG-1 and found that the mutant ALG-1(anti) protein fails to interact with numerous miRISC cofactors, including proteins known to be necessary for target repression. In addition, alg-1(anti) mutants dramatically overaccumulated microRNA* (passenger) strands, and immunoprecipitated ALG-1(anti) complexes contained nonstoichiometric yields of mature microRNA and microRNA* strands, with some microRNA* strands present in the ALG-1(anti) Argonaute far in excess of the corresponding mature microR...Continue Reading

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Citations

Jun 22, 2018·PLoS Genetics·Antti P AaltoAmy E Pasquinelli
Sep 22, 2020·Wiley Interdisciplinary Reviews. RNA·Jeffrey C MedleyAnna Y Zinovyeva
Dec 16, 2018·Nature Communications·Amanda L MinogueSwathi Arur
Dec 4, 2019·Briefings in Bioinformatics·Fabian KernAndreas Keller
Feb 16, 2021·G3 : Genes - Genomes - Genetics·Dustin Haskell, Anna Zinovyeva

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