Abstract
Argonaute proteins are often credited for their cytoplasmic activities in which they function as central mediators of the RNAi platform and microRNA (miRNA)-mediated processes. They also facilitate heterochromatin formation and establishment of repressive epigenetic marks in the nucleus of fission yeast and plants. However, the nuclear functions of Ago proteins in mammalian cells remain elusive. In the present study, we combine ChIP-seq (chromatin immunoprecipitation coupled with massively parallel sequencing) with biochemical assays to show that nuclear Ago1 directly interacts with RNA Polymerase II and is widely associated with chromosomal loci throughout the genome with preferential enrichment in promoters of transcriptionally active genes. Additional analyses show that nuclear Ago1 regulates the expression of Ago1-bound genes that are implicated in oncogenic pathways including cell cycle progression, growth, and survival. Our findings reveal the first landscape of human Ago1-chromosomal interactions, which may play a role in the oncogenic transcriptional program of cancer cells.
Highlights
Argonautes (Ago) comprise a family of evolutionarily conserved proteins that are central to the RNA interference (RNAi) platform and miRNA function [1,2]
Nuclear localization and distribution of Ago1 and Ago2 We have previously shown that Ago1 and Ago2 exist in the nuclear fraction of mouse cells [11]
To determine if this feature is conserved in human cells, we examined Ago1 and Ago2 cellular
Summary
Argonautes (Ago) comprise a family of evolutionarily conserved proteins that are central to the RNA interference (RNAi) platform and miRNA function [1,2]. Ago proteins are often recognized by their cytoplasmic function in which they regulate gene transcripts via post-transcriptional gene silencing (PTGS) mechanisms. Nuclear functions have been well-characterized in fission yeast and plants in which they assist in mechanisms of transcriptional gene silencing (TGS). Ago partners with antisense transcripts to form the RITS (RNA-induced transcriptional silencing) complex at centromeric regions to induce heterochromatin formation [3]. Our data represents the first landscape of Ago1-chromosomal interactions in human cells and reveals a novel function for Ago in modulating gene transcription within the nucleus
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
