Two isoforms of the essential C. elegans Argonaute CSR-1 differentially regulate sperm and oocyte fertility.

Autor:	Charlesworth AG; Department of Molecular Genetics, University of Toronto Toronto, ON M5S 1A8 Canada., Seroussi U; Department of Molecular Genetics, University of Toronto Toronto, ON M5S 1A8 Canada., Lehrbach NJ; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Renaud MS; Department of Molecular Genetics, University of Toronto Toronto, ON M5S 1A8 Canada., Sundby AE; Department of Molecular Genetics, University of Toronto Toronto, ON M5S 1A8 Canada., Molnar RI; Department of Molecular Genetics, University of Toronto Toronto, ON M5S 1A8 Canada., Lao RX; Department of Molecular Genetics, University of Toronto Toronto, ON M5S 1A8 Canada., Willis AR; Department of Molecular Genetics, University of Toronto Toronto, ON M5S 1A8 Canada., Woock JR; Department of Molecular Genetics, University of Toronto Toronto, ON M5S 1A8 Canada., Aber MJ; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Diao AJ; Department of Molecular Genetics, University of Toronto Toronto, ON M5S 1A8 Canada., Reinke AW; Department of Molecular Genetics, University of Toronto Toronto, ON M5S 1A8 Canada., Ruvkun G; Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA., Claycomb JM; Department of Molecular Genetics, University of Toronto Toronto, ON M5S 1A8 Canada.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2021 Sep 07; Vol. 49 (15), pp. 8836-8865.
DOI:	10.1093/nar/gkab619
Abstrakt:	The Caenorhabditis elegans genome encodes nineteen functional Argonaute proteins that use 22G-RNAs, 26G-RNAs, miRNAs or piRNAs to regulate target transcripts. Only one Argonaute is essential under normal laboratory conditions: CSR-1. While CSR-1 has been studied widely, nearly all studies have overlooked the fact that the csr-1 locus encodes two isoforms. These isoforms differ by an additional 163 amino acids present in the N-terminus of CSR-1a. Using CRISPR-Cas9 genome editing to introduce GFP::3xFLAG into the long (CSR-1a) and short (CSR-1b) isoforms, we found that CSR-1a is expressed during spermatogenesis and in several somatic tissues, including the intestine. CSR-1b is expressed constitutively in the germline. small RNA sequencing of CSR-1 complexes shows that they interact with partly overlapping sets of 22G-RNAs. Phenotypic analyses reveal that the essential functions of csr-1 described in the literature coincide with CSR-1b, while CSR-1a plays tissue specific functions. During spermatogenesis, CSR-1a integrates into an sRNA regulatory network including ALG-3, ALG-4 and WAGO-10 that is necessary for fertility at 25°C. In the intestine, CSR-1a silences immunity and pathogen-responsive genes, and its loss results in improved survival from the pathogen Pseudomonas aeruginosa. Our findings functionally distinguish the CSR-1 isoforms and highlight the importance of studying each AGO isoform independently. (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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