Lin28调控let-7 microRNA合成机制的研究进展

Research Progress in Molecular Mechanism of Lin28 Mediated let-7 miRNA Regulation

Lin28是在胚胎干细胞中广泛表达的RNA结合蛋白,参与分化、发育、肿瘤发生、葡萄糖代谢等多个生命过程。Lin28执行这些功能主要是通过抑制let-7 miRNA的生物合成,并且主要依赖Lin28氨基端冷休克结构域和羧基端锌指结构域。最近一些结构学研究揭示了Lin28调控let-7合成机制,Lin28结合在pri-let-7和pre-let-7的末端loop上,从而阻断Drosha和Dicer的加工,这些互作的特异性主要由锌指结构域和保守的GGAG模体介导。本文就Lin28如何通过其结构域与let-7miRNA前体特异性结合,特异性结合的结构基础等进行了综述,以期为相关研究提供借鉴。

Lin28is an essential RNA-binding protein that is ubiquitously expressed in embryonic stem cells.Its physiological function has been linked to the regulation of differentiation,development,oncogenesis,and glucose metabolism.Lin28 mediates these functions by inhibiting let-7 miRNA biogenesis and this activity depends on Lin28＇s amino terminal carboxyl terminal cold shock domain（CSD）and zink knuckle domain（ZKD）.Recently,biochemical and structural studies revealed the mechanisms of how Lin28 control let-7biogenesis.Lin28 binds to the terminal loop of pri-and pre-let-7miRNA and represses their processing by Drosha and Dicer.The specificity of this interaction is mainly mediated by the ZKD with a conserved GGAG.In this paper,we reviewed the specific interaction and structural basis between Lin28 and precursors of let-7.