Graduate School of Biomedical Sciences; Program in Molecular Medicine; Program in Gene Function and Expression
Medical Subject Headings
Amino Acid Sequence; Animals; Binding Sites; Caenorhabditis elegans; *Gene Expression Regulation, Developmental; *Genes, Helminth; MicroRNAs; Molecular Sequence Data; RNA Interference; Sequence Homology, Amino Acid; Transcription Factors
Life Sciences | Medicine and Health Sciences
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-48andmir-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.
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Citation: Genes Dev. 2008 Sep 15;22(18):2520-34. Link to article on publisher's site
Genes and development
Ow, Maria C.; Martinez, Natalia Julia; Olsen, Philip H.; Silverman, Howard S.; Barrasa, M. Inmaculada; Conradt, Barbara; Walhout, Albertha J. M.; and Ambros, Victor R., "The FLYWCH transcription factors FLH-1, FLH-2, and FLH-3 repress embryonic expression of microRNA genes in C. elegans" (2008). GSBS Student Publications. 1351.