The potential functions of primary microRNAs in target recognition and repression.
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.
Trujillo
Robin Deis
RD
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Yue
Si-Biao
SB
Tang
Yujie
Y
O'Gorman
William E
WE
Chen
Chang-Zheng
CZ
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*
D035683:MicroRNAs; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human
Nature. 2000 Feb 24;403(6772):901-6
10706289
RNA. 2008 Aug;14(8):1539-49
18566191
J Cell Biol. 2008 Jul 14;182(1):61-76
18625843
Chem Biol. 2004 Dec;11(12):1619-23
15610845
Nature. 2008 Sep 4;455(7209):58-63
18668040
Annu Rev Microbiol. 1994;48:713-42
7826024
Cell. 2003 Dec 26;115(7):787-98
14697198
J Mol Biol. 1974 Sep 5;88(1):165-74
4613840
Nature. 2008 Sep 4;455(7209):64-71
18668037
PLoS One. 2008;3(10):e3592
18974849
Science. 2002 Sep 20;297(5589):2056-60
12154197
Science. 2008 Apr 4;320(5872):97-100
18292307
RNA. 2008 May;14(5):829-35
18367718
Genes Dev. 2003 Feb 15;17(4):438-42
12600936
Annu Rev Biochem. 1991;60:631-52
1715680
Cell. 2006 Dec 15;127(6):1193-207
17174894
Cell. 2007 Mar 23;128(6):1105-18
17382880
Nat Rev Mol Cell Biol. 2005 May;6(5):376-85
15852042
Nat Genet. 2006 Jun;38 Suppl:S8-13
16736023
J Biol Chem. 1994 Nov 4;269(44):27486-93
7961663
Genes Dev. 2004 Mar 1;18(5):504-11
15014042
Cell. 1993 Dec 3;75(5):843-54
8252621