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Bracht, JR, Van Wynsberghe, PM, Mondol, V and Pasquinelli, AE (2010) Regulation of lin-4 miRNA expression, organismal growth and development by a conserved RNA binding protein in C. elegans. Dev. Biol. 348:210-21
Transcription and multiple processing steps are required to produce specific 22 nucleotide microRNAs (miRNAs) that can regulate the expression of target genes. In C. elegans, mature lin-4 miRNA accumulates at the end of the first larval stage to repress its direct targets lin-14 and lin-28, allowing the progression of several somatic cell types to later larval fates. In this study, we characterized the expression of endogenous lin-4 and found that temporally regulated independent transcripts, but not constitutive lin-4 containing RNAs derived from an overlapping gene, are processed to mature lin-4 miRNA. Through an RNAi screen, we identified a conserved RNA binding protein gene rbm-28 (R05H10.2), homologous to the human RBM28 and yeast Nop4p proteins, that is important for lin-4 expression in C. elegans. We also demonstrate that rbm-28 genetically interacts with the lin-4 developmental timing pathway and uncover a previously unrecognized role for lin-14 and lin-28 in coordinating organismal growth.
Animals; Animals, Genetically Modified; Caenorhabditis elegans/embryology; Caenorhabditis elegans/genetics; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Conserved Sequence; Gene Expression Regulation, Developmental; MicroRNAs/metabolism; RNA, Helminth/metabolism; RNA-Binding Proteins/genetics; RNA-Binding Proteins/metabolism
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