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 lin-28 in coordinating organismal growth.

Research Highlights►Expression of the C. elegans lin-4 miRNA is supported by temporally regulated independent transcripts, but not constitutive lin-4 containing RNAs derived from an overlapping gene. ►A conserved RNA binding protein gene rbm-28 (R05H10.2), homologous to the human RBM28 and yeast Nop4p proteins, regulates the accumulation of mature lin-4 miRNA in C. elegans. ►rbm-28 genetically interacts with the lin-4 developmental timing pathway. ►rbm-28 regulates organismal growth.