Graduate School of Biomedical Sciences; Program in Molecular Medicine; Program in Gene Function and Expression
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.
DOI of Published Version
Genes Dev. 2008 Sep 15;22(18):2520-34. Link to article on publisher's site
Genes and development
Ow MC, Martinez NJ, Olsen PH, Silverman HS, Barrasa MI, Conradt B, Walhout AJ, Ambros VR. (2008). The FLYWCH transcription factors FLH-1, FLH-2, and FLH-3 repress embryonic expression of microRNA genes in C. elegans. GSBS Student Publications. https://doi.org/10.1101/gad.1678808. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1351