RNA结合蛋白Lin28研究获进展 [复制链接]

温州大学金建钰、雷新响这两位年轻教师在美国耶鲁大学黄英群博士指导下完成最新论文，报道了有关Lin28和RNA解旋酶A（RHA）之间的分子作用特性的新成果，这对于了解Lin28在miRNA表达的调节、骨骼肌及心肌分化、肿瘤形成、多能性诱导等多种有关发育的事件中的作用具有重要意义。这一研究成果公布在国际著名期刊《核酸研究》（Nucleic Acids Research）（核酸研究，影响因子: 7.479）上。



这篇论文是温州大学金建钰、雷新响这两位年轻教师在美国耶鲁大学黄英群博士指导下完成的，文章的第一作者金建钰老师2009年以访问助理教授的身份在美国耶鲁大学医学院进行生物化学与分子生物学方向的研究。文章第三作者雷新响也是温州大学分析测试中心教师。



Lin28是一种高度保守的RNA结合蛋白，它在miRNA表达的调节、骨骼肌及心肌分化、肿瘤形成、多能性诱导等多种有关发育的事件中起着重要作用。这篇文章报道了Lin28和RNA解旋酶A（RHA）之间的分子作用特性，Lin28通过积极地招募RHA到多核糖体来促进翻译，这些研究对于分析Lin28的关键作用具有重要的意义。



Lin28最早发现于秀丽隐杆线虫中，是一种高度保守的RNA结合蛋白，参与线虫发育时序调控。Lin28基因突变可以打乱线虫发育进程的顺序，Lin28/let-7通路参与了多种生物功能，包括干细胞功能及肿瘤的发生，因此对于这一分子机制的研究有助于分析相关的病理原因。



之前就曾有科学家对30个候选基因进行了一项RNA干涉筛选，结果发现Lin28（let-7，microRNA处理的一个负调控因子）是原始生殖细胞发育的一个潜在关键调控因子--这是发育中的胚胎内所发生的一个过程，它选择注定要产生精子和卵子的细胞。而且Lin28水平在原发性人类生殖细胞肿瘤中升高，说明它或许也与生殖细胞恶性肿瘤有关。

Evidence that Lin28 stimulates translation by recruiting RNA helicase A to polysomes

Jianyu Jin1,2,
Wei Jing3,
Xin-Xiang Lei1,2,
Chen Feng1,4,
Shuping Peng1,
Kathleen Boris-Lawrie3 and
Yingqun Huang1,*

+ Author Affiliations

1Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510 USA, 2Department of Chemistry, College of Teacher Education, Wenzhou University, Wenzhou, Zhejiang 325035, China, 3Department of Veterinary Biosciences, Center for RNA Biology, Center for Retrovirus Research, Ohio State University, Columbus, OH 43210 USA and 4Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, Liaoning 110001, China

*To whom correspondence should be addressed. Tel: +1 203 737 2578; Fax: +1 203 785 7134; Email: yingqun.huang@yale.edu
Received November 23, 2010.
Revision received December 21, 2010.
Accepted December 22, 2010.


Abstract

The stem cell protein Lin28 functions to inhibit the biogenesis of a group of miRNAs but also stimulates the expression of a subset of mRNAs at the post-transcriptional level, the underlying mechanism of which is not yet understood. Here we report the characterization of the molecular interplay between Lin28 and RNA helicase A (RHA) known to play an important role in remodeling ribonucleoprotein particles during translation. We show that reducing Lin28 expression results in decreased RHA association with polysomes while increasing Lin28 expression leads to elevated RHA association. Further, the carboxyl terminus of Lin28 is necessary for interaction with both the amino and carboxyl termini of RHA. Importantly, a carboxyl terminal deletion mutant of Lin28 that retains RNA-binding activity fails to interact with RHA and exhibits dominant-negative effects on Lin28-dependent stimulation of translation. Taken together, these results lead us to su ggest that Lin28 may stimulate translation by actively recruiting RHA to polysomes.
© The Author(s) 2011. Published by Oxford University Press.


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