title: The potential functions of primary microRNAs in target recognition and repression.
abstract: Major RNA products of a microRNA (miRNA) gene--the long primary transcript (pri-miRNA), the ∼70-nucleotide (nt) precursor miRNA (pre-miRNA), and the ∼21-nt mature miRNA--all contain the same sequence required for target gene recognition. Thus, it is intrinsically difficult to discern the contribution of individual RNA species or to rule out a function of miRNA precursor species in target repression. Here, we describe a novel approach to dissect the functional contribution of pri-miRNA without compromising important cellular pathways. We show that pri-let-7 has a direct function in target repression in the absence of properly processed mature let-7. Moreover, we show that loop nucleotides provide regulatory controls of the activity of pri-let-7 by modulating interactions between pri-let-7 and target RNAs in vitro and in vivo. Finally, we show that human let-7a-3 pri-miRNA can directly interact with target mRNAs. These findings illustrate that the regulatory information encoded in structured pri-miRNAs may be translated into function through direct interactions with target mRNAs.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Robin Deis
authors.initials: RD
authors.lastname: Trujillo
authors.forename: Si-Biao
authors.initials: SB
authors.lastname: Yue
authors.forename: Yujie
authors.initials: Y
authors.lastname: Tang
authors.forename: William E
authors.initials: WE
authors.lastname: O'Gorman
authors.forename: Chang-Zheng
authors.initials: CZ
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D017173:Caenorhabditis elegans; D002460:Cell Line; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human
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