A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye.
A critical question about signal transduction is how weak or transient activation of signaling pathways achieves a robust and long-term switch in gene expression. We report that a microRNA is part of a mechanism that makes cells sensitive to signals in the Drosophila eye. Expression of miR-7 is activated in cells as they begin differentiating into photoreceptors. This is dependent on EGF receptor (EGFR) signaling that triggers ERK-mediated degradation of the transcription factor Yan. In nonstimulated cells, Yan represses miR-7 transcription, whereas miR-7 RNA represses Yan protein expression in photoreceptors, by binding to sequences within its mRNA 3'UTR. We propose that reciprocal negative feedback between Yan and miR-7 ensures mutually exclusive expression, with Yan in progenitor cells and miR-7 in photoreceptor cells. Expression is switched when EGFR signaling transiently triggers Yan degradation. This two-tiered mechanism explains how signal transduction activity can robustly generate a stable change in gene-expression patterns.
Li
Xin
X
Department of Biochemistry, Molecular Biology and Cell Biology, 2205 Tech Drive, Northwestern University, Evanston, Illinois 60208, USA.
Carthew
Richard W
RW
D000818:Animals; D002454:Cell Differentiation; D017124:Conserved Sequence; D004330:Drosophila; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005123:Eye / Q000166:cytology*; D005136:Eye Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016678:Genome; D035683:MicroRNAs / Q000378:metabolism* / Q000494:pharmacology; D008954:Models, Biological; D009154:Mutation; D010786:Photoreceptor Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014158:Transcription, Genetic
C076188:AOP protein, Drosophila; D029721:Drosophila Proteins; D005136:Eye Proteins; D035683:MicroRNAs; D012097:Repressor Proteins; D066246:ErbB Receptors