title: Direct transcriptional regulation by nuclear microRNAs.
abstract: The function of microRNAs is well characterized in the cytoplasm, where they direct an Argonaute-containing complex to target and repress mRNAs. More recently, regulatory roles for microRNAs and Argonaute have also been reported in the nucleus where microRNAs guide Argonaute to target gene promoters and directly regulate transcription in either a positive or a negative manner. Deep sequencing has revealed a high abundance of endogenous microRNAs within the nucleus, and in silico target prediction suggests thousands of potential microRNA:promoter interaction sites. The predicted high frequency of miRNA:promoter interactions is supported by chromatin immunoprecipitation, indicating the microRNA-dependent recruitment of Argonaute to thousands of transcriptional start sites and the subsequent regulation of RNA polymerase-II occupancy and chromatin modifiers. In this review we discuss the evidence for, and mechanisms associated with, direct transcriptional regulation by microRNAs which may represent a significant and largely unexplored aspect of microRNA function. This article is part of a Directed Issue entitled: The non-coding RNA revolution.
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, Australia.
authors.forename: Marika
authors.initials: M
authors.lastname: Salmanidis
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, Australia.
authors.forename: Katherine
authors.initials: K
authors.lastname: Pillman
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, Australia; Discipline of Medicine, University of Adelaide, Adelaide, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
authors.forename: Gregory
authors.initials: G
authors.lastname: Goodall
authors.affiliation: Centre for Cancer Biology, University of South Australia, Adelaide, Australia; Discipline of Medicine, University of Adelaide, Adelaide, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia. Electronic address: cameron.bracken@health.sa.gov.au.
authors.forename: Cameron
authors.initials: C
authors.lastname: Bracken
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Argonaute; RNA activation; RNA interference; Transcriptional regulation; microRNA