GSBS Student Publications

UMMS Affiliation

Graduate School of Biomedical Sciences; Program in Molecular Medicine; Program in Gene Function and Expression

Date

9-17-2008

Document Type

Article

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

Disciplines

Life Sciences | Medicine and Health Sciences

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-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.

Rights and Permissions

Citation: Genes Dev. 2008 Sep 15;22(18):2520-34. Link to article on publisher's site

DOI of Published Version

10.1101/gad.1678808

Related Resources

Link to Article in PubMed

Journal Title

Genes and development

PubMed ID

18794349

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