The FLYWCH transcription factors FLH-1, FLH-2, and FLH-3 repress embryonic expression of microRNA genes in C. elegans

• Published in: Genes & development Vol. 22; no. 18; pp. 2520 - 2534
• Main Authors: Ow, Maria C, Martinez, Natalia J, Olsen, Philip H, Silverman, Howard S, Barrasa, M Inmaculada, Conradt, Barbara, Walhout, Albertha J M, Ambros, Victor
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 15.09.2008
• Subjects: Amino Acid Sequence; Animals; Binding Sites; Caenorhabditis elegans; Caenorhabditis elegans - embryology; Caenorhabditis elegans - genetics; Gene Expression Regulation, Developmental; Genes, Helminth; MicroRNAs - genetics; Molecular Sequence Data; Research Paper; RNA Interference; Sequence Homology, Amino Acid; Transcription Factors - chemistry; Transcription Factors - metabolism; Transcription Factors - physiology
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.1678808

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.