microRNAs are endogenously expressed ∼21 nucleotide noncoding RNAs. microRNA-mediated regulation of the translation of specific mRNA is implicated in a range of developmental processes and pathologies. As such, miRNA expression is tightly controlled in normal development by both transcriptional and post-transcriptional mechanisms. This chapter is concerned with the control of pre-miRNA processing of individual miRNAs by specific factors. It is focussed on the regulation of a subset of miRNAs by the RNA-binding protein Lin28/LIN-28. We discuss how Lin28/LIN-28 can sequester pre-let-7 miRNA precursor to prevent Dicer-mediated processing. We describe how interaction of pre-let-7 with Lin28/ LIN-28 leads to pre-let-7 uridylation and subsequent degradation. Finally, we analyze how let-7 and Lin28/LIN-28 together act as a highly conserved developmental switch that controls stem cell differentiation in C. elegans and mammals.
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