Wellcome Trust Cancer Research UK Gurdon Institute and Department of Biochemistry, University of Cambridge, The Henry Wellcome Building of Cancer and Developmental Biology, Tennis Court Rd, Cambridge CB2 1QN, UK.
Adv Exp Med Biol. 2010;700:67-75.
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 21 个核苷酸的非编码 RNA。microRNA 介导的特定 mRNA 翻译的调节参与了一系列的发育过程和病理学。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。本章涉及特定因子对单个 miRNA 的前体 miRNA 加工的控制。它主要关注 RNA 结合蛋白 Lin28/LIN-28 对一组 miRNA 的调节。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 如何协同作用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。
