Mechanisms of Lin28-mediated miRNA and mRNA regulation--a structural and functional perspective.
Mechanisms of Lin28-mediated miRNA and mRNA regulation--a structural and functional perspective.
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DOI：
10.3390/ijms140816532
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发表时间：
2013-08-09
影响因子：
5.6
通讯作者：
Heinemann U
中科院分区：
文献类型：
--
作者：
Mayr F;Heinemann U
LIN28是一种重要的RNA结合蛋白，在胚胎干细胞中广泛表达。它的生理功能与分化、发育、肿瘤发生和葡萄糖代谢的调节有关。LIN28通过抑制let-7miRNA的生物发生和调节靶mRNAs的翻译来介导这些多效性功能。这两种活性都强烈依赖于LIN28‘端的S RNA结合域(RBDS)、N端的冷休克结构域(CSD)和C端的锌指节域(ZKD)。最近的生化和结构研究揭示了Lin28如何控制let-7生物发生的机制。LIN28与Pri-和Pre-let-7miRNA的末端环结合，并通过DROSHA和DICER抑制它们的加工。一些生化和结构研究表明，这种相互作用的特异性主要是由具有保守的GGAGA或GGAGA样基序的ZKD介导的。进一步的RNA交联和免疫沉淀结合高通量测序(CLIP-SEQ)研究证实了这一结合基序，并发现了大量新的mRNA结合位点。在这里，我们回顾了令人兴奋的最新进展，我们对Lin28如何结合结构上不同的RNA并实现其多效性功能的理解。
Lin28 is 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, and oncogenesis as well as glucose metabolism. Lin28 mediates these pleiotropic functions by inhibiting let-7 miRNA biogenesis and by modulating the translation of target mRNAs. Both activities strongly depend on Lin28’s RNA-binding domains (RBDs), an N-terminal cold-shock domain (CSD) and a C-terminal Zn-knuckle domain (ZKD). Recent biochemical and structural studies revealed the mechanisms of how Lin28 controls let-7 biogenesis. Lin28 binds to the terminal loop of pri- and pre-let-7 miRNA and represses their processing by Drosha and Dicer. Several biochemical and structural studies showed that the specificity of this interaction is mainly mediated by the ZKD with a conserved GGAGA or GGAGA-like motif. Further RNA crosslinking and immunoprecipitation coupled to high-throughput sequencing (CLIP-seq) studies confirmed this binding motif and uncovered a large number of new mRNA binding sites. Here we review exciting recent progress in our understanding of how Lin28 binds structurally diverse RNAs and fulfills its pleiotropic functions.
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影响因子：
4.1
作者：
Graf R;Munschauer M;Mastrobuoni G;Mayr F;Heinemann U;Kempa S;Rajewsky N;Landthaler M
通讯作者：
Landthaler M
影响因子：
4.5
作者：
Hafner, Markus;Max, Klaas E. A.;Tuschl, Thomas
通讯作者：
Tuschl, Thomas
影响因子：
14.9
作者：
Jaroszewski L;Li Z;Cai XH;Weber C;Godzik A
通讯作者：
Godzik A
影响因子：
64.5
作者：
Heo, Inha;Joo, Chirlmin;Kim, V. Narry
通讯作者：
Kim, V. Narry
影响因子：
5.2
作者：
Darr, Henia;Benvenisty, Nissim
通讯作者：
Benvenisty, Nissim