Pluto Bioinformatics

GSE39652: AGO4 Regulates Entry into Meiosis and Influences Silencing of Sex Chromosomes in the Male Mouse Germline

Bulk RNA sequencing

The four mammalian Argonaute family members are thought to share redundant functions in the microRNA pathway, yet only AGO2 possesses the catalytic "slicer" function required for RNA; interference. Whether AGO1, AGO3, or AGO4 possess specialized functions remains unclear. Here, we Series_summary = show that AGO4 localizes to spermatocyte nuclei during meiotic prophase I, specifically at sites of asynapsis and in the transcriptionally silenced XY sub-domain, the sex body. We generated Ago4 knockout mice and show that Ago4-/- spermatogonia initiate meiosis early, resulting from premature; induction of retinoic acid-response genes. During prophase I, the sex body assembles incorrectly in Ago4-/- mice, leading to disrupted meiotic sex chromosome inactivation (MSCI). This is associated; with a dramatic loss of microRNAs, >20% of which arise from the X chromosome. Loss of AGO4 results in increased AGO3 in spermatocytes, indicating some degree of redundancy. Thus, AGO4 regulates; meiotic entry and MSCI in mammalian germ cells, implicating small RNA pathways in these processes. SOURCE: Stephanie,Renee,Hilz (stephanie.hilz@gmail.com) - Cornell University