专题:Nature报道
在真核生物中,很多基因都含有一个或多个“内含子”,即作为mRNA一部分被转录、但在mRNA被翻译成蛋白之前被除掉的序列。在前体mRNA(pre-mRNA)中适当位置剪接这些“内含子”的大分子机器被称为“剪接体”。它由被称为snRNPs(核内小核糖核蛋白 ,或称“snurps”)的几个RNA-蛋白复合体及其他非snRNP蛋白组成。
现在,U1 snRNP(它在“内含子”的5\'端组装,是与一个pre-mRNA结合的第一个snurp)的结构已被以5.5Å的分辨率确定。由该结构所反映的这一亚单元内的相互作用,显示了“内含子”的起始端是怎样被U1 snRNP识别、从而使其被“剪接体”剪去的。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 458, 475-480 (26 March 2009) | doi:10.1038/nature07851
Crystal structure of human spliceosomal U1 snRNP at 5.5 Å resolution
Daniel A. Pomeranz Krummel1,2,3, Chris Oubridge1,3, Adelaine K. W. Leung1,2, Jade Li1 & Kiyoshi Nagai1
1 MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
2 Present addresses: Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02454-9110, USA (D.A.P.K.); Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA (A.K.W.L.).
3 These authors contributed equally to this work.
Correspondence to: Kiyoshi Nagai1 Correspondence and requests for materials should be addressed to K.N.
Human spliceosomal U1 small nuclear ribonucleoprotein particles (snRNPs), which consist of U1 small nuclear RNA and ten proteins, recognize the 5' splice site within precursor messenger RNAs and initiate the assembly of the spliceosome for intron excision. An electron density map of the functional core of U1 snRNP at 5.5 Å resolution has enabled us to build the RNA and, in conjunction with site-specific labelling of individual proteins, to place the seven Sm proteins, U1-C and U1-70K into the map. Here we present the detailed structure of a spliceosomal snRNP, revealing a hierarchical network of intricate interactions between subunits. A striking feature is the amino (N)-terminal polypeptide of U1-70K, which extends over a distance of 180 ? from its RNA binding domain, wraps around the core domain consisting of the seven Sm proteins and finally contacts U1-C, which is crucial for 5'-splice-site recognition. The structure of U1 snRNP provides insights into U1 snRNP assembly and suggests a possible mechanism of 5'-splice-site recognition.