Upregulation of the let-7 microRNA with precocious development in lin-12/Notch hypermorphic Caenorhabditis elegans mutants.
The lin-12/Notch signaling pathway is conserved from worms to humans and is a master regulator of metazoan development. Here, we demonstrate that lin-12/Notch gain-of-function (gf) animals display precocious alae at the L4 larval stage with a significant increase in let-7 expression levels. Furthermore, lin-12(gf) animals display a precocious and higher level of let-7 gfp transgene expression in seam cells at L3 stage. Interestingly, lin-12(gf) mutant rescued the lethal phenotype of let-7 mutants similar to other known heterochronic mutants. We propose that lin-12/Notch signaling pathway functions in late developmental timing, upstream of or in parallel to the let-7 heterochronic pathway. Importantly, the human microRNA let-7a was also upregulated in various human cell lines in response to Notch 1 activation, suggesting an evolutionarily conserved cross-talk between let-7 and the canonical lin-12/Notch signaling pathway.
Solomon
Aharon
A
Division of Molecular Oncology, Evanston Northwestern Healthcare Research Institute, Department of Medicine, Feinberg School of Medicine, USA.
Mian
Yousaf
Y
Ortega-Cava
Cesar
C
Liu
Victor Won Tat
VW
Gurumurthy
Channabasavaiah Basavaraju
CB
Naramura
Mayumi
M
Band
Vimla
V
Band
Hamid
H
D000818:Animals; D030801:Animals, Genetically Modified; D015152:Blotting, Northern; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000235:genetics; D007814:Larva; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D010641:Phenotype; D051880:Receptors, Notch / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D035683:MicroRNAs; D051880:Receptors, Notch; C474488:let-7 microRNA, C elegans; D049452:Green Fluorescent Proteins