title: A role for microRNAs in the Drosophila circadian clock.
abstract: Little is known about the contribution of translational control to circadian rhythms. To address this issue and in particular translational control by microRNAs (miRNAs), we knocked down the miRNA biogenesis pathway in Drosophila circadian tissues. In combination with an increase in circadian-mediated transcription, this severely affected Drosophila behavioral rhythms, indicating that miRNAs function in circadian timekeeping. To identify miRNA-mRNA pairs important for this regulation, immunoprecipitation of AGO1 followed by microarray analysis identified mRNAs under miRNA-mediated control. They included three core clock mRNAs-clock (clk), vrille (vri), and clockworkorange (cwo). To identify miRNAs involved in circadian timekeeping, we exploited circadian cell-specific inhibition of the miRNA biogenesis pathway followed by tiling array analysis. This approach identified miRNAs expressed in fly head circadian tissue. Behavioral and molecular experiments show that one of these miRNAs, the developmental regulator bantam, has a role in the core circadian pacemaker. S2 cell biochemical experiments indicate that bantam regulates the translation of clk through an association with three target sites located within the clk 3' untranslated region (UTR). Moreover, clk transgenes harboring mutated bantam sites in their 3' UTRs rescue rhythms of clk mutant flies much less well than wild-type CLK transgenes.
authors.affiliation: National Center for Behavioral Genomics and Department of Biology, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kadener
authors.forename: Jerome S
authors.initials: JS
authors.lastname: Menet
authors.forename: Ken
authors.initials: K
authors.lastname: Sugino
authors.forename: Michael D
authors.initials: MD
authors.lastname: Horwich
authors.forename: Uri
authors.initials: U
authors.lastname: Weissbein
authors.forename: Pipat
authors.initials: P
authors.lastname: Nawathean
authors.forename: Vasia V
authors.initials: VV
authors.lastname: Vagin
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Zamore
authors.forename: Sacha B
authors.initials: SB
authors.lastname: Nelson
authors.forename: Michael
authors.initials: M
authors.lastname: Rosbash
mesh_terms: D020413:3' Untranslated Regions / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001665:Binding Sites; D056926:CLOCK Proteins; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D015870:Gene Expression; D005786:Gene Expression Regulation; D006257:Head / Q000502:physiology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034743:RNA-Induced Silencing Complex / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C120526:Clk protein, Drosophila; D029721:Drosophila Proteins; D035683:MicroRNAs; D012333:RNA, Messenger; D034743:RNA-Induced Silencing Complex; D014157:Transcription Factors; C471146:bantam microRNA, Drosophila; D056926:CLOCK Proteins
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19291-6
references.pmid: 18042700
references.citation: Cell. 2007 Jul 27;130(2):287-97
references.pmid: 17662943
references.citation: BMC Neurosci. 2002;3:1
references.pmid: 11825337
references.citation: Mol Cell Biol. 2001 Feb;21(4):1207-17
references.pmid: 11158307
references.citation: FEBS Lett. 2009 Mar 18;583(6):1039-44
references.pmid: 19236868
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17719-24
references.pmid: 17965236
references.citation: Nature. 2004 Oct 14;431(7010):862-8
references.pmid: 15483615
references.citation: PLoS Biol. 2008 May 20;6(5):e119
references.pmid: 18494558
references.citation: J Biol Chem. 2007 Aug 24;282(34):25053-66
references.pmid: 17597072
references.citation: Neuron. 2007 Jun 7;54(5):813-29
references.pmid: 17553428
references.citation: Nature. 2002 Dec 19-26;420(6917):816-20
references.pmid: 12447397
references.citation: Nature. 2007 Jul 12;448(7150):151-6
references.pmid: 17625558
references.citation: Nature. 2009 Jul 23;460(7254):479-86
references.pmid: 19536157
references.citation: Cell. 2003 Apr 4;113(1):25-36
references.pmid: 12679032
references.citation: Genes Dev. 2007 Jul 1;21(13):1687-700
references.pmid: 17578908
references.citation: Genes Dev. 2009 Jun 1;23(11):1313-26
references.pmid: 19487572
references.citation: Curr Biol. 2002 Aug 6;12(15):1331-5
references.pmid: 12176363
references.citation: RNA. 2007 Dec;13(12):2324-9
references.pmid: 17928574
references.citation: EMBO J. 1992 Jan;11(1):1-6
references.pmid: 1740100
references.citation: Curr Biol. 2007 Jun 19;17(12):1082-9
references.pmid: 17555964
references.citation: Cell. 2003 Feb 7;112(3):329-41
references.pmid: 12581523
references.citation: Development. 2005 Nov;132(21):4645-52
references.pmid: 16224044
references.citation: Cell. 2004 Apr 2;117(1):69-81
references.pmid: 15066283
references.citation: Adv Genet. 2003;48:1-280
references.pmid: 12593455
references.citation: Neuron. 2001 Nov 20;32(4):657-71
references.pmid: 11719206
references.citation: BMC Genomics. 2008 Feb 19;9:83
references.pmid: 18284684
references.citation: Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2260-4
references.pmid: 8134384
references.citation: Curr Biol. 2003 Apr 29;13(9):790-5
references.pmid: 12725740
references.citation: Curr Biol. 2007 Sep 18;17(18):R789-93
references.pmid: 17878043
references.citation: Cell. 1999 Dec 23;99(7):791-802
references.pmid: 10619432
references.citation: Genes Dev. 2004 Jul 15;18(14):1655-66
references.pmid: 15231716
references.citation: PLoS One. 2008 May 07;3(5):e2126
references.pmid: 18461144
references.citation: Science. 2001 Sep 21;293(5538):2251-6
references.pmid: 11567138
references.citation: RNA. 2007 Aug;13(8):1198-204
references.pmid: 17592038
references.citation: Science. 2008 May 23;320(5879):1077-81
references.pmid: 18403677
references.citation: PLoS Comput Biol. 2005 Jun;1(1):e13
references.pmid: 16103902
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: Nature. 2005 Nov 10;438(7065):238-42
references.pmid: 16281038
references.citation: Science. 1994 Mar 18;263(5153):1603-6
references.pmid: 8128246
references.citation: Science. 1995 Nov 3;270(5237):808-10
references.pmid: 7481772
references.citation: Cell. 2001 Nov 30;107(5):567-78
references.pmid: 11733057
references.citation: Genes Dev. 2006 Mar 15;20(6):723-33
references.pmid: 16543224
references.citation: EMBO J. 2003 Jul 1;22(13):3367-75
references.pmid: 12839998
references.citation: Cell. 2009 Apr 17;137(2):273-82
references.pmid: 19379693
references.citation: J Comp Neurol. 2000 Jun 19;422(1):66-94
references.pmid: 10842219
references.citation: Genes Dev. 2005 Dec 1;19(23):2837-48
references.pmid: 16287716
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12457-62
references.pmid: 16895995
references.citation: Genes Dev. 2007 Jul 1;21(13):1675-86
references.pmid: 17578907
references.citation: Science. 2005 Jan 14;307(5707):251-4
references.pmid: 15550625
references.citation: Cell. 1998 May 29;93(5):791-804
references.pmid: 9630223
references.citation: Neuron. 2003 Jan 23;37(2):249-61
references.pmid: 12546820
references.citation: Genesis. 2002 Sep-Oct;34(1-2):1-15
references.pmid: 12324939
references.citation: RNA. 2009 Apr;15(4):537-45
references.pmid: 19223442
references.citation: Nature. 1990 Feb 8;343(6258):536-40
references.pmid: 2105471
references.citation: Cell. 1998 May 29;93(5):805-14
references.pmid: 9630224
references.citation: Genetics. 2000 Oct;156(2):665-75
references.pmid: 11014814