RRC ID 4274
Author Ow MC, Martinez NJ, Olsen PH, Silverman HS, Barrasa MI, Conradt B, Walhout AJ, Ambros V.
Title The FLYWCH transcription factors FLH-1, FLH-2, and FLH-3 repress embryonic expression of microRNA genes in C. elegans.
Journal Genes Dev.
Abstract MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally via antisense base-pairing. Although miRNAs are involved in a variety of important biological functions, little is known about their transcriptional regulation. Using yeast one-hybrid assays, we identified transcription factors with a FLYWCH Zn-finger DNA-binding domain that bind to the promoters of several Caenorhabditis elegans miRNA genes. The products of the flh-1 and flh-2 genes function redundantly to repress embryonic expression of lin-4, mir-48, and mir-241, miRNA genes that are normally expressed only post-embryonically. Although single mutations in either flh-1 or flh-2 genes result in a viable phenotype, double mutation of flh-1 and flh-2 results in early larval lethality and an enhanced derepression of their target miRNAs in embryos. Double mutations in flh-2 and a third FLYWCH Zn-finger-containing transcription factor, flh-3, also result in enhanced precocious expression of target miRNAs. Mutations of lin-4 or mir-48&mir-241 do not rescue the lethal flh-1; flh-2 double-mutant phenotype, suggesting that the inviability is not solely the result of precocious expression of these miRNAs. Therefore, the FLH-1 and FLH-2 proteins likely play a more general role in regulating gene expression in embryos.
Volume 22(18)
Pages 2520-34
Published 2008-9-15
DOI 10.1101/gad.1678808
PII 22/18/2520
PMID 18794349
PMC PMC2546698
MeSH Amino Acid Sequence Animals Binding Sites Caenorhabditis elegans / embryology Caenorhabditis elegans / genetics* Gene Expression Regulation, Developmental* Genes, Helminth* MicroRNAs / genetics* Molecular Sequence Data RNA Interference Sequence Homology, Amino Acid Transcription Factors / chemistry Transcription Factors / metabolism Transcription Factors / physiology*
IF 9.462
Times Cited 30
C.elegans tm2118 tm2126 tm3024