title: Dampening of expression oscillations by synchronous regulation of a microRNA and its target.
abstract: The complexity of multicellular organisms requires precise spatiotemporal regulation of gene expression during development. We find that in the nematode Caenorhabditis elegans approximately 2,000 transcripts undergo expression oscillations synchronized with larval transitions while thousands of genes are expressed in temporal gradients, similar to known timing regulators. By counting transcripts in individual worms, we show that pulsatile expression of the microRNA (miRNA) lin-4 maintains the temporal gradient of its target lin-14 by dampening its expression oscillations. Our results demonstrate that this insulation is optimal when pulsatile expression of the miRNA and its target is synchronous. We propose that such a miRNA-mediated incoherent feed-forward loop is a potent filter that prevents the propagation of potentially deleterious fluctuations in gene expression during the development of an organism.
authors.affiliation: 1] Department of Physics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. [3].
authors.forename: Dong hyun
authors.initials: Dh
authors.lastname: Kim
authors.forename: Dominic
authors.initials: D
authors.lastname: Grün
authors.forename: Alexander
authors.initials: A
authors.lastname: van Oudenaarden
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C102669:LIN-14 protein, C elegans; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; C452194:lin-4 microRNA, C elegans
references.citation: Dev Biol. 1977 Mar;56(1):110-56
references.pmid: 838129
references.citation: Nature. 2005 Feb 17;433(7027):769-73
references.pmid: 15685193
references.citation: Nat Methods. 2008 Oct;5(10):877-9
references.pmid: 18806792
references.citation: Genome Res. 2008 Dec;18(12):2005-15
references.pmid: 18981266
references.citation: Cell. 1993 Dec 3;75(5):843-54
references.pmid: 8252621
references.citation: Science. 1999 Nov 5;286(5442):1141-6
references.pmid: 10550049
references.citation: Science. 2010 Dec 24;330(6012):1775-87
references.pmid: 21177976
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D918-23
references.pmid: 22086951
references.citation: Evol Dev. 2002 Jan-Feb;4(1):16-27
references.pmid: 11871396
references.citation: Nature. 1989 Mar 23;338(6213):313-9
references.pmid: 2922060
references.citation: Curr Biol. 2010 Dec 21;20(24):2159-68
references.pmid: 21129974
references.citation: Bioinformatics. 2010 Mar 1;26(5):589-95
references.pmid: 20080505
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6355-60
references.pmid: 15096621
references.citation: Proc Natl Acad Sci U S A. 2011 Nov 1;108(44):17997-8002
references.pmid: 22011579
references.citation: Nat Rev Genet. 2007 Jun;8(6):450-61
references.pmid: 17510665
references.citation: WormBook. 2007 Mar 19;:1-15
references.pmid: 18050497
references.citation: Dev Biol. 2004 Feb 15;266(2):399-416
references.pmid: 14738886
references.citation: Bioinformatics. 2007 Jan 15;23(2):257-8
references.pmid: 17098774
references.citation: Genes Dev. 1987 Jun;1(4):398-414
references.pmid: 3678829
references.citation: Cell. 1997 Mar 7;88(5):637-46
references.pmid: 9054503
references.citation: Nature. 2005 Mar 24;434(7032):462-9
references.pmid: 15791247
references.citation: Cell. 1989 Apr 7;57(1):49-57
references.pmid: 2702689
references.citation: PLoS Biol. 2005 Oct;3(10):e312
references.pmid: 16122351
references.citation: Cell. 1993 Dec 3;75(5):855-62
references.pmid: 8252622
references.citation: Nature. 2008 Sep 4;455(7209):58-63
references.pmid: 18668040
references.citation: Genetics. 1989 Mar;121(3):501-16
references.pmid: 2565854
references.citation: EMBO J. 1996 Jul 15;15(14):3633-9
references.pmid: 8670866
references.citation: Cell. 2009 Jan 23;136(2):215-33
references.pmid: 19167326
references.citation: Development. 2005 Sep;132(17):3787-98
references.pmid: 16100088
references.citation: Science. 1984 Oct 26;226(4673):409-16
references.pmid: 6494891
references.citation: Cell. 2005 Jan 14;120(1):15-20
references.pmid: 15652477
references.citation: Nat Methods. 2008 Jul;5(7):621-8
references.pmid: 18516045
references.citation: Cell. 2008 Oct 17;135(2):216-26
references.pmid: 18957198
references.citation: WormBook. 2005 Sep 01;:1-4
references.pmid: 18050415
references.citation: Cell Metab. 2012 Apr 4;15(4):439-50
references.pmid: 22482727
references.citation: Genetics. 2001 Jan;157(1):199-209
references.pmid: 11139502
references.citation: Nature. 2008 Jan 31;451(7178):569-72
references.pmid: 18185515
references.citation: Mol Cell. 2007 Jun 8;26(5):753-67
references.pmid: 17560377
references.citation: Cell. 2005 Aug 26;122(4):553-63
references.pmid: 16122423
references.citation: Nature. 2008 Sep 4;455(7209):64-71
references.pmid: 18668037
references.citation: Mol Cell. 2000 Apr;5(4):659-69
references.pmid: 10882102
references.citation: Dev Biol. 1999 Jun 1;210(1):87-95
references.pmid: 10364429
references.citation: Curr Biol. 2010 Feb 23;20(4):367-73
references.pmid: 20096582
references.citation: J Mol Biol. 1990 Oct 5;215(3):403-10
references.pmid: 2231712
references.citation: Dev Biol. 2010 Aug 15;344(2):603-10
references.pmid: 20493184