院士Nature文章miRNAs前瞻性研究成果

　　

生物通报道，加州大学圣地亚哥分校（UCSD）医学院霍华休斯研究所（HHMI）、意大利国立癌症研究所、英国国立医学研究所联合瑞士Friedrich Miescher研究所的人员在最新的Nature发表microRNAs的研究进展，The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs。

 

文章通讯作者是HHMI的研究员、美国科学院院士Michael G. Rosenfeld，他主要从事基因组学、表观遗传学及各种信号通路研究。

 

microRNAs是一种调控基因表达的重要非编码RNA，它对机体的胚胎发育、生长等多种生理过程具有重要的调控作用，并且对癌症的发生也具有重要的作用。然而，目前的研究主要集中在microRNAs对基因调控方面的研究，对microRNAs自身的生物合成等方面的研究却极少。

 

本文正是对microRNA的前体pri-miRNA的生物合成进行研究。RNA结合蛋白KSRP（“KH-型剪接调控蛋白”的缩写）调控一个亚组的微RNA的前体加工。如果这一调控机制被破坏，其效应在增殖、分化和凋亡上就可以被看到。所以，KSRP既参与mRNA的周转，又参与促进mRNA的表达。这项工作揭示了mi-RNA在调控基因表达上的复杂性的另一个层面。

（生物通 小茜）

生物通推荐原文检索：The RNA-binding protein KSRP promotes the biogenesis of a subset of microRNAs

Michele Trabucchi1, Paola Briata2,5, MariaFlor Garcia-Mayoral3, Astrid D. Haase4, Witold Filipowicz4, Andres Ramos3, Roberto Gherzi2,5 & Michael G. Rosenfeld1,5

 

Howard Hughes Medical Institute, Department and School of Medicine, University of California, San Diego, 9500 Gilman Drive, Room 345, La Jolla, California 92093-0648, USA

Istituto Nazionale per la Ricerca sul Cancro (IST), Largo R. Benzi, 10; 16132 Genova, Italy

Division of Molecular Structure, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK

Friedrich Miescher Institute for Biomedical Research, PO Box 2543, 4002 Basel, Switzerland

These authors contributed equally to this work.

 

【Abstract】

Consistent with the role of microRNAs (miRNAs) in down-regulating gene expression by reducing the translation and/or stability of target messenger RNAs1, the levels of specific miRNAs are important for correct embryonic development and have been linked to several forms of cancer2, 3, 4. However, the regulatory mechanisms by which primary miRNAs (pri-miRNAs) are processed first to precursor miRNAs (pre-miRNAs) and then to mature miRNAs by the multiprotein Drosha and Dicer complexes5, 6, 7, 8, respectively, remain largely unknown. The KH-type splicing regulatory protein (KSRP, also known as KHSRP) interacts with single-strand AU-rich-element-containing mRNAs and is a key mediator of mRNA decay9, 10. Here we show in mammalian cells that KSRP also serves as a component of both Drosha and Dicer complexes and regulates the biogenesis of a subset of miRNAs. KSRP binds with high affinity to the terminal loop of the target miRNA precursors and promotes their maturation. This mechanism is required for specific changes in target mRNA expression that affect specific biological programs, including proliferation, apoptosis and differentiation. These findings reveal an unexpected mechanism that links KSRP to the machinery regulating maturation of a cohort of miRNAs that, in addition to its role in promoting mRNA decay, independently serves to integrate specific regulatory programs of protein expression.