, .
Adv Exp Med Biol. 2011;700:67-75. doi: 10.1007/978-1-4419-7823-3_7.
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.
microRNAs 是内源性表达的约 21 个核苷酸的非编码 RNA。miRNA 介导的特定 mRNA 翻译调控参与了一系列发育过程和病理。因此，miRNA 的表达在正常发育过程中受到转录和转录后机制的严格控制。本章关注的是特定因子对单个 miRNA 的前体 miRNA 加工的控制。它专注于 RNA 结合蛋白 Lin28/LIN-28 对一组 miRNA 的调控。我们讨论了 Lin28/LIN-28 如何将 pre-let-7 miRNA 前体隔离，以防止 Dicer 介导的加工。我们描述了 pre-let-7 与 Lin28/LIN-28 的相互作用如何导致 pre-let-7 的尿苷酸化和随后的降解。最后，我们分析了 let-7 和 Lin28/LIN-28 如何共同作为一个高度保守的发育开关，控制线虫和哺乳动物中的干细胞分化。
