title: Systematic analysis of dynamic miRNA-target interactions during C. elegans development.
abstract: Although microRNA (miRNA)-mediated functions have been implicated in many aspects of animal development, the majority of miRNA::mRNA regulatory interactions remain to be characterized experimentally. We used an AIN/GW182 protein immunoprecipitation approach to systematically analyze miRNA::mRNA interactions during C. elegans development. We characterized the composition of miRNAs in functional miRNA-induced silencing complexes (miRISCs) at each developmental stage and identified three sets of miRNAs with distinct stage-specificity of function. We then identified thousands of miRNA targets in each developmental stage, including a significant portion that is subject to differential miRNA regulation during development. By identifying thousands of miRNA family-mRNA pairs with temporally correlated patterns of AIN-2 association, we gained valuable information on the principles of physiological miRNA::target recognition and predicted 1589 high-confidence miRNA family::mRNA interactions. Our data support the idea that miRNAs preferentially target genes involved in signaling processes and avoid genes with housekeeping functions, and that miRNAs orchestrate temporal developmental programs by coordinately targeting or avoiding genes involved in particular biological functions.
authors.affiliation: Howard Hughes Medical Institute and Department of MCDB, University of Colorado, Boulder, CO 80309, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Molly
authors.initials: M
authors.lastname: Hammell
authors.forename: Brian A
authors.initials: BA
authors.lastname: Kudlow
authors.forename: Victor
authors.initials: V
authors.lastname: Ambros
authors.forename: Min
authors.initials: M
authors.lastname: Han
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C525939:AIN-2 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins
references.citation: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W472-6
references.pmid: 16845052
references.citation: EMBO Rep. 2006 Sep;7(9):904-10
references.pmid: 16906129
references.citation: Nat Struct Mol Biol. 2006 Sep;13(9):849-51
references.pmid: 16921378
references.citation: WormBook. 2006 Jun 02;:1-4
references.pmid: 18050439
references.citation: J Cell Biol. 2006 Jul 31;174(3):349-58
references.pmid: 16880270
references.citation: Bioinformatics. 2005 Jul 1;21(13):2988-93
references.pmid: 15840702
references.citation: Nature. 2005 Mar 17;434(7031):338-45
references.pmid: 15735639
references.citation: PLoS Biol. 2003 Dec;1(3):E60
references.pmid: 14691535
references.citation: Dev Cell. 2005 Mar;8(3):321-30
references.pmid: 15737928
references.citation: Nat Struct Mol Biol. 2007 Apr;14(4):287-94
references.pmid: 17401373
references.citation: Nat Methods. 2008 Sep;5(9):813-9
references.pmid: 19160516
references.citation: Nature. 2003 Dec 18;426(6968):845-9
references.pmid: 14685240
references.citation: Nat Methods. 2009 Jun;6(6):397-8
references.pmid: 19478799
references.citation: Genes Dev. 2003 Apr 15;17(8):991-1008
references.pmid: 12672692
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10838-43
references.pmid: 11005858
references.citation: Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W460-4
references.pmid: 15980512
references.citation: Nat Struct Mol Biol. 2008 Apr;15(4):346-53
references.pmid: 18345015
references.citation: Nature. 2000 Feb 24;403(6772):901-6
references.pmid: 10706289
references.citation: Dev Cell. 2003 May;4(5):639-50
references.pmid: 12737800
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D354-7
references.pmid: 16381885
references.citation: Dev Cell. 2005 Sep;9(3):415-22
references.pmid: 16139229
references.citation: RNA. 2005 Nov;11(11):1640-7
references.pmid: 16177138
references.citation: Cell. 2006 Dec 15;127(6):1193-207
references.pmid: 17174894
references.citation: Cell. 1998 May 15;93(4):519-29
references.pmid: 9604928
references.citation: Science. 2001 Sep 21;293(5538):2269-71
references.pmid: 11486053
references.citation: Nat Rev Mol Cell Biol. 2008 Mar;9(3):219-30
references.pmid: 18270516
references.citation: Cell. 2008 May 30;133(5):903-15
references.pmid: 18510933
references.citation: Cell. 2005 Mar 11;120(5):635-47
references.pmid: 15766527
references.citation: Trends Genet. 1997 Sep;13(9):375-6
references.pmid: 9287494
references.citation: Nat Cell Biol. 2005 Dec;7(12):1261-6
references.pmid: 16284623
references.citation: Cell. 1997 Mar 7;88(5):637-46
references.pmid: 9054503
references.citation: Nature. 2000 Nov 2;408(6808):86-9
references.pmid: 11081512
references.citation: Nat Genet. 2006 Jun;38 Suppl:S8-13
references.pmid: 16736023
references.citation: Nat Cell Biol. 2005 Dec;7(12):1267-74
references.pmid: 16284622
references.citation: Nat Genet. 2000 May;25(1):25-9
references.pmid: 10802651
references.citation: Nat Genet. 2007 Oct;39(10):1278-84
references.pmid: 17893677
references.citation: PLoS Genet. 2007 Dec;3(12):e215
references.pmid: 18085825
references.citation: Nat Genet. 2002 Apr;30(4):363-4
references.pmid: 11896390
references.citation: Genes Dev. 2004 Mar 1;18(5):504-11
references.pmid: 15014042
references.citation: Cell. 1993 Dec 3;75(5):843-54
references.pmid: 8252621
references.citation: Cell. 2006 Jun 16;125(6):1111-24
references.pmid: 16777601
references.citation: Dev Cell. 2005 Sep;9(3):403-14
references.pmid: 16139228
references.citation: Dev Cell. 2003 May;4(5):625-37
references.pmid: 12737799
references.citation: Cell. 1993 Dec 3;75(5):855-62
references.pmid: 8252622
references.citation: Cell. 2001 Jul 13;106(1):23-34
references.pmid: 11461699
references.citation: Cell. 2002 Jun 28;109(7):861-71
references.pmid: 12110183
references.citation: Nature. 2004 Aug 12;430(7001):785-9
references.pmid: 15306811
references.citation: Nature. 2008 Sep 4;455(7209):58-63
references.pmid: 18668040
references.citation: Genetics. 1974 May;77(1):71-94
references.pmid: 4366476
references.citation: Mol Cell. 2005 Aug 19;19(4):437-47
references.pmid: 16109369
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14863-8
references.pmid: 9843981
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: EMBO J. 2009 Feb 4;28(3):213-22
references.pmid: 19131968
references.citation: Cell. 2005 Jan 14;120(1):15-20
references.pmid: 15652477
references.citation: PLoS Biol. 2005 Mar;3(3):e85
references.pmid: 15723116
references.citation: Nature. 2004 Sep 16;431(7006):350-5
references.pmid: 15372042
references.citation: Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):974-9
references.pmid: 9927678
references.citation: Cell. 2003 Dec 26;115(7):787-98
references.pmid: 14697198
references.citation: Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14385-9
references.pmid: 16983084
references.citation: Curr Opin Struct Biol. 2005 Oct;15(5):490-8
references.pmid: 16154350
references.citation: Genes Dev. 2006 Jul 15;20(14):1885-98
references.pmid: 16815998
references.citation: Annu Rev Cell Dev Biol. 2007;23:175-205
references.pmid: 17506695
references.citation: J Biol Chem. 1999 Aug 13;274(33):22915-8
references.pmid: 10438455
references.citation: Cell. 2005 Dec 16;123(6):1133-46
references.pmid: 16337999
references.citation: Mol Cell. 2007 Nov 30;28(4):598-613
references.pmid: 18042455
references.citation: Curr Biol. 2006 Nov 7;16(21):2135-42
references.pmid: 17084698
references.citation: Science. 2005 Nov 25;310(5752):1330-3
references.pmid: 16239437