2011年1月9日，《自然·結(jié)構(gòu)和分子生物學(xué)》（Nature Structural & Molecular Biology）在線發(fā)表了浙江大學(xué)生命科學(xué)學(xué)院金勇豐課題組原創(chuàng)性研究成果：應(yīng)用RNA物理競爭原理,，數(shù)學(xué)模型結(jié)合分子生物學(xué)方法破解了RNA互斥剪接的調(diào)控機(jī)制，并闡明了最復(fù)雜的Dscam等基因的可變剪接的調(diào)控機(jī)制,，該機(jī)制可能普遍適用于不同生物和基因。以前人們大多認(rèn)為mRNA以線型的形式出現(xiàn),，該發(fā)現(xiàn)展示了美麗的mRNA結(jié)構(gòu)動態(tài)及其新調(diào)控功能,。被審稿專家認(rèn)為“The experiments provide the clearest evidence to date for the formation and function of long range secondary structures”。上述工作完全由金勇豐課題組在國內(nèi)實驗室完成,。
可變剪接是產(chǎn)生蛋白質(zhì)和功能的多樣性的重要途徑,，對細(xì)胞分化和發(fā)育以及疾病發(fā)生等至關(guān)重要。人類高達(dá)95%以上的基因是可變剪接的,。這種可變剪接產(chǎn)生的產(chǎn)物數(shù)目是極其驚人的,，如果蠅Dscam(唐氏綜合癥細(xì)胞黏附分子)基因通過互斥剪接可產(chǎn)生的異構(gòu)體多達(dá)38 016種，是其整個基因組基因數(shù)目的兩倍,。但是,，對其產(chǎn)生機(jī)制并不清楚。由于Dscam等基因與神經(jīng)和免疫功能等相關(guān),，該研究成果不僅對深入認(rèn)識基因表達(dá)的調(diào)控機(jī)制，而且對闡析疾病發(fā)生發(fā)展機(jī)制具有十分重要的意義,。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature Structural & Molecular Biology doi:10.1038/nsmb.1959
RNA secondary structure in mutually exclusive splicing
Yun Yang,1, 3 Leilei Zhan,1, 3 Wenjing Zhang,1, 3 Feng Sun,1 Wenfeng Wang,1 Nan Tian,1 Jingpei Bi,1 Haitao Wang,1 Dike Shi,1 Yajian Jiang,1 Yaozhou Zhang2 & Yongfeng Jin1
Mutually exclusive splicing is a regulated means to generate protein diversity, but the underlying mechanisms are poorly understood. Here comparative genome analysis revealed the built-in intronic elements for controlling mutually exclusive splicing of the 14-3-3ξ pre-mRNA. These elements are clade specific but are evolutionarily conserved at the secondary structure level. Combined evidence revealed the triple functions of these inter-intronic RNA pairings in synergistically ensuring the selection of only one of multiple exons, through activation of the proximal variable exon outside the loop by the approximation of cis elements, and simultaneous repression of the exon within the loop, in combination with the physical competition of RNA pairing. Additionally, under this model, we also deciphered a similar structural code in exon clusters 4 and 9 of Dscam (38,016 isoforms) and Mhc (480 isoforms). Our findings suggest a broadly applicable mechanism to ensure mutually exclusive splicing.
