Regulation of lin-4 miRNA expression, organismal growth and development by a conserved RNA binding protein in C elegans

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 fin 28 in coordinating organismal growth (C) 2010 Elsevier Inc All rights reserved