BioProject

Argonaute 2 (AGO2) is a cytoplasmic component of the miRNA pathway with essential roles in development and disease. More...

Argonaute 2 (AGO2) is a cytoplasmic component of the miRNA pathway with essential roles in development and disease. Yet, little is known about its regulation in vivo. Here, we show that in mouse quiescent cells, AGO2 localizes almost exclusively to the nucleus. In quiescent splenocytes, AGO2’s subcellular localization is modulated by the Pi3K-AKT-mTOR pathway, a well-established regulator of quiescence. Signaling through this pathway in proliferating cells promotes AGO2 cytoplasmic accumulation at least in part by stimulating the expression of TNRC6, an AGO2 binding partner in the miRNA pathway. In contrast, low signaling in quiescent cells enables AGO2 to accumulate in the nucleus where it binds to young mobile transposons co-transcriptionally. Loss of AGO2 in quiescent cells results in upregulation of transposon transcripts suggesting it performs functions analogous to those of PIWI in the germline. Our results point to an essential but previously unrecognized nuclear role for AGO2 during mammalian quiescence as part of a genome-defense system against transposable elements. Overall design: small RNA sequencing following immunopercipitation of AGO2 using an antibody against the HA epitope in Ago2HA/HA mice. Less...