Reference Report

Reference
Citation	Lai, E.C., Tam, B., Rubin, G.M. (2005). Pervasive regulation of Drosophila Notch target genes by GY-box-, Brd-box-, and K-box-class microRNAs. Genes Dev. 19(9): 1067--1080.
FlyBase ID	FBrf0187594
Type of publication	Research paper
Offprint Available	No
External Crossreferences
PubMed ID	15833912
PubMed Abstract	Although hundreds of distinct animal microRNAs (miRNAs) are known, the specific biological functions of only a handful are understood at present. Here, we demonstrate that three different families of Drosophila miRNAs directly regulate two large families of Notch target genes, including basic helix-loop-helix (bHLH) repressor and Bearded family genes. These miRNAs regulate Notch target gene activity via GY-box (GUCUUCC), Brd-box (AGCUUUA), and K-box (cUGUGAUa) motifs. These are conserved sites in target 3'-untranslated regions (3'-UTRs) that are complementary to the 5'-ends of miRNAs, or "seed" regions. Collectively, these motifs represent >40 miRNA-binding sites in Notch target genes, and we show all three classes of motif to be necessary and sufficient for miRNA-mediated regulation in vivo. Importantly, many of the validated miRNA-binding sites have limited pairing to miRNAs outside of the "box:seed" region. Consistent with this, we find that seed-related miRNAs that are otherwise quite divergent can regulate the same target sequences. Finally, we demonstrate that ectopic expression of several Notch-regulating miRNAs induces mutant phenotypes that are characteristic of Notch pathway loss of function, including loss of wing margin, thickened wing veins, increased bristle density, and tufted bristles. Collectively, these data establish insights into miRNA target recognition and demonstrate that the Notch signaling pathway is a major target of miRNA-mediated regulation in Drosophila.
Biosis	2005.10079203
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Language of publication	English
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Abbreviation	Genes Dev.
Title	Genes & Development
Authors
Volume range	1-
Year range	1987-
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Publisher
Place of publication	Cold Spring Harbor, NY
Language of publication	English
ISBN/ISSN	0890-9369
CODEN	GEDEEP
Data from Reference
Alleles (43)
	Avic\GFP^{EGFP.Bob.3'UTR.αTub84B} Avic\GFP^{EGFP.Bob.GYmut.αTub84B} Avic\GFP^{EGFP.Bob.GYwt.αTub84B} Avic\GFP^{EGFP.Brd.Brdmut.αTub84B} Avic\GFP^{EGFP.Brd.Brdwt.αTub84B} Avic\GFP^{EGFP.E(spl).Kbox.αTub84B} Avic\GFP^{EGFP.HLHm3.3'UTR.αTub84B} Avic\GFP^{EGFP.HLHm5.3'UTR.3xGYmut.αTub84B} Avic\GFP^{EGFP.HLHm5.3'UTR.αTub84B} Avic\GFP^{EGFP.HLHmγ.3'UTR.αTub84B} Avic\GFP^{EGFP.HLHmδ.3'UTR.αTub84B} Avic\GFP^{EGFP.Ocho.3'UTR.αTub84B} Avic\GFP^{EGFP.Tom.3'UTR.αTub84B} Avic\GFP^{EGFP.m4.3'UTR.αTub84B} Avic\GFP^{EGFP.mir-5.αTub84B} Avic\GFP^{EGFP.mir-7.αTub84B} Avic\GFP^{EGFP.mα.3'UTR.αTub84B} Avic\GFP^{EGFP.αTub84B.B} Brd^{3xBrd+GYmut.arm.T:Avic\GFP-YFP} Brd^{GYmut.arm.T:Avic\GFP-YFP} Brd^{arm.T:Avic\GFP-YFP} Ecol\lacZ^{arm.1.8.Brd.wt} Ecol\lacZ^{arm.1.8.E(spl).wt} Scer\GAL4^Bx-MS1096 Scer\GAL4^dpp.blk1 T:Avic\GFP^YFP T:Disc\RFP^DsRed2 mir-11^{Scer\UAS.T:Disc\RFP-DsRed2} mir-286^{Scer\UAS.T:Disc\RFP-DsRed2} mir-2a-1^Scer\UAS.cLa mir-2a-1^{mir2.Scer\UAS.T:Disc\RFP-DsRed2} mir-2a-2^Scer\UAS.cLa mir-2a-2^{mir2.Scer\UAS.T:Disc\RFP-DsRed2} mir-2b-2^Scer\UAS.cLa mir-2b-2^{mir2.Scer\UAS.T:Disc\RFP-DsRed2} mir-4^{Scer\UAS.T:Disc\RFP-DsRed2} mir-5^{Scer\UAS.T:Disc\RFP-DsRed2} mir-6-1^Scer\UAS.cLa mir-6-2^Scer\UAS.cLa mir-6-3^Scer\UAS.cLa mir-79^{Scer\UAS.T:Disc\RFP-DsRed2} mir-7^{Scer\UAS.T:Disc\RFP-DsRed2} mir-7^Scer\UAS.cLa
Constructs (29)
	P{GAL4-dpp.blk1} P{Tub-EGFP.B} P{UAS-DsRed2-mir-11} P{UAS-DsRed2-mir-286.mir-4.mir-5} P{UAS-DsRed2-mir-2} P{UAS-DsRed2-mir-79} P{UAS-DsRed2-mir-7} P{UAS-mir-2.L} P{UAS-mir-6.L} P{UAS-mir-7.L} P{arm-YFP.Brd3'UTR.3xBrd+GYmut} P{arm-YFP.Brd3'UTR.GYmut} P{arm-YFP.Brd3'UTR} P{tub-EGFP.Bob.3'UTR} P{tub-EGFP.Bob.GYmut} P{tub-EGFP.Bob.GYwt} P{tub-EGFP.Brd.Brdmut} P{tub-EGFP.Brd.Brdwt} P{tub-EGFP.E(spl).Kbox} P{tub-EGFP.HLHm5.3'UTR.3xGYmut} P{tub-EGFP.HLHm5.3'UTR} P{tub-EGFP.HLHmγ.3'UTR} P{tub-EGFP.HLHmδ.3'UTR} P{tub-EGFP.Ocho.3'UTR} P{tub-EGFP.Tom.3'UTR} P{tub-EGFP.m4.3'UTR} P{tub-EGFP.mir-5} P{tub-EGFP.mir-7} P{tub-EGFP.mα.3'UTR}
Genes (44)
	Avic\GFP BobA BobB BobC Brd Dpse\BobA Dpse\BobB Dpse\BobC Dpse\Brd Dpse\HLHm5 Dpse\m4 Dpse\malpha Dvir\Brd Dvir\HLHm5 Dvir\HLHmδ Dvir\Ocho E(spl) Ecol\lacZ HLHm3 HLHm5 HLHm7 HLHmβ HLHmγ HLHmδ N Ocho Scer\GAL4 Tom m2 m4 m6 mir-11 mir-286 mir-2a-1 mir-2a-2 mir-2b-2 mir-4 mir-5 mir-6-1 mir-6-2 mir-6-3 mir-7 mir-79 mα
Natural transposons (1)
	P-element