title: Regulation of microRNA-mediated gene silencing by microRNA precursors.
abstract: Processing of microRNAs (miRNAs) from their precursors to their biologically active mature forms is regulated during development and cancer. We show that mouse pri- or pre-miR-151 can bind to and compete with mature miR-151-5p and miR-151-3p for binding sites contained within the complementary regions of the E2f6 mRNA 3' untranslated region (UTR). E2f6 mRNA levels were directly regulated by pri- or pre-miR-151. Conversely, miR-151-mediated repression of ARHGDIA mRNA was dependent on the level of mature miR-151 because only the mature miRNA binds the 3' UTR. Thus, processing of miR-151 can have different effects on separate mRNA targets within a cell. A bioinformatics pipeline revealed additional candidate regions where precursor miRNAs can compete with their mature miRNA counterparts. We validated this experimentally for miR-124 and the SNAI2 3' UTR. Hence, miRNA precursors can serve as post-transcriptional regulators of miRNA activity and are not mere biogenesis intermediates.
authors.affiliation: 1] Department of Pediatrics, Stanford University, Stanford, California, USA. [2] Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Biswajoy
authors.initials: B
authors.lastname: Roy-Chaudhuri
authors.affiliation: 1] Department of Pediatrics, Stanford University, Stanford, California, USA. [2] Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Valdmanis
authors.affiliation: 1] Department of Pediatrics, Stanford University, Stanford, California, USA. [2] Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1] Department of Pediatrics, Stanford University, Stanford, California, USA. [2] Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 1] Department of Pediatrics, Stanford University, Stanford, California, USA. [2] Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Qing-Jun
authors.initials: QJ
authors.lastname: Luo
authors.affiliation: 1] Department of Pediatrics, Stanford University, Stanford, California, USA. [2] Department of Genetics, Stanford University, Stanford, California, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Kay
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D050701:E2F6 Transcription Factor / Q000235:genetics*; D005260:Female; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D050701:E2F6 Transcription Factor; C111236:E2f6 protein, mouse; C582434:MIRN151 microRNA, mouse; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D012333:RNA, Messenger; C000604408:SNAI2 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors
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