PMID- 15833912
OWN - NLM
STAT- MEDLINE
DCOM- 20050617
LR  - 20220223
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 19
IP  - 9
DP  - 2005 May 1
TI  - Pervasive regulation of Drosophila Notch target genes by GY-box-, Brd-box-, and 
      K-box-class microRNAs.
PG  - 1067-80
AB  - 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.
FAU - Lai, Eric C
AU  - Lai EC
AD  - Department of Molecular and Cell Biology/Howard Hughes Medical Institute, 
      University of California at Berkeley, Berkeley, CA 94720-3200, USA. 
      lai@fruitfly.org
FAU - Tam, Bergin
AU  - Tam B
FAU - Rubin, Gerald M
AU  - Rubin GM
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050415
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Brd protein, Drosophila)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (N protein, Drosophila)
RN  - 0 (Receptors, Notch)
RN  - 0 (Transcription Factors)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - 3' Untranslated Regions/metabolism
MH  - Amino Acid Motifs/*genetics
MH  - Animals
MH  - Base Pairing
MH  - Base Sequence
MH  - Basic Helix-Loop-Helix Transcription Factors
MH  - Cloning, Molecular
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Drosophila/genetics/*metabolism
MH  - Drosophila Proteins/genetics/metabolism
MH  - Fluorescent Antibody Technique
MH  - Gene Components
MH  - *Gene Expression Regulation
MH  - Green Fluorescent Proteins
MH  - Membrane Proteins/genetics/*metabolism
MH  - MicroRNAs/genetics/*metabolism
MH  - Molecular Sequence Data
MH  - Multigene Family/genetics
MH  - *Phenotype
MH  - Receptors, Notch
MH  - Signal Transduction/genetics/*physiology
MH  - Transcription Factors/genetics/metabolism
MH  - Transgenes/genetics
PMC - PMC1091741
EDAT- 2005/04/19 09:00
MHDA- 2005/06/18 09:00
PMCR- 2005/11/01
CRDT- 2005/04/19 09:00
PHST- 2005/04/19 09:00 [pubmed]
PHST- 2005/06/18 09:00 [medline]
PHST- 2005/04/19 09:00 [entrez]
PHST- 2005/11/01 00:00 [pmc-release]
AID - gad.1291905 [pii]
AID - 00191067 [pii]
AID - 10.1101/gad.1291905 [doi]
PST - ppublish
SO  - Genes Dev. 2005 May 1;19(9):1067-80. doi: 10.1101/gad.1291905. Epub 2005 Apr 15.