Abstract
Argonaute 2 (AGO2) is a ubiquitously expressed protein critical for regulation of mRNA translation and vital to animal development. AGO2 protein is found in both cytoplasmic and nuclear compartments, and although its cytoplasmic role is well studied, the biological relevance of nuclear AGO2 is unclear. Here, we address this problem in vivo using spermatogenic cells as a model. We find that AGO2 transiently binds both chromatin and nucleus-specific mRNA transcripts of hundreds of genes required for sperm production during male meiosis in mice, and that germline conditional knockout (cKO) of Ago2 causes depletion of the encoded proteins. Correspondingly, Ago2 cKO males show abnormal sperm head morphology and reduced sperm count, along with reduced postnatal viability of offspring. Together, our data reveal an unexpected nuclear role for AGO2 in enhancing expression of developmentally important genes during mammalian male reproduction.
Funder
Yale University
National Institutes of Health (NIH) Scientific Interest Groups
Yale Center for Genome Analysis
Edward P. Evans Foundation
NIH/National Institute of Diabetes and Digestive and Kidney Diseases
NIDDK
NIH/NIDDK
Cooperative Centers of Excellence in Hematology
Yale CCEH
Associazione Italiana per la Ricerca sul Cancro
Yale University School of Medicine
NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development
Searle Scholars Program
Pew Charitable Trusts
Burroughs Wellcome Fund
Publisher
Cold Spring Harbor Laboratory
Subject
Genetics (clinical),Genetics
Cited by
8 articles.
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