Seeking the truth behind the myth: Argonaute tales from ??nuclearland??

NAZER, E.; GÓMEZ ACUÑA, L. I.; KORNBLIHTT, A. R.

MOLECULAR CELL

CELL PRESS

Lugar: United States; Año: 2022

1097-2765

Argonaute proteins have been traditionally characterized as a highly evolutionary conserved family engagedin post-transcriptional gene silencing pathways. The Argonaute family is mainly grouped into the AGO andPIWI clades. The canonical role of Argonaute proteins relies on their ability to bind small-RNAs that recognizecomplementary sequences on target mRNAs to induce either mRNA degradation or translational repression.However, there is an increasing amount of evidence supporting that Argonaute proteins also exert multiplenuclear functions that subsequently regulate gene expression. In this line, genome-wide studies showed thatmembers from the AGO clade regulate transcription, 3D chromatin organization, and splicing of active locilocated within euchromatin. Here, we discuss recent work based on high-throughput technologies thathave significantly contributed to shed light on the multivariate nuclear functions of AGO proteins in differentmodel organisms. We also analyze data supporting that AGO proteins are able to execute these nuclear func-tions independently from small RNA pathways. Finally, we integrate these mechanistic insights with recentreports highlighting the clinical importance of AGO in breast and prostate cancer development.