RT Journal
A1 Griffin, Kimberly N.
A1 Walters, Benjamin William
A1 Li, Haixin
A1 Wang, Huafeng
A1 Biancon, Giulia
A1 Tebaldi, Toma
A1 Kaya, Carolyn B.
A1 Kanyo, Jean
A1 Lam, TuKiet T.
A1 Cox, Andy L.
A1 Halene, Stephanie
A1 Chung, Jean-Ju
A1 Lesch, Bluma J.
T1 Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction
JF Genome Research 
JO Genome Research 
YR 2022 
FD September 01 
VO 32 
IS 9 
SP 1655 
OP 1668 
DO 10.1101/gr.276578.122 
UL http://genome.cshlp.org/content/32/9/1655.abstract 
AB 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.