總所周知,，一部電影包含數(shù)千個隨機(jī)的場景,，如果沒有出色的編輯,，那么播放的東西將可能是毫無意義的。同樣的,，組成我們基因組DNA的RNA“卷軸”也需要被仔細(xì)的“編輯”,。
由基因組成的有意義序列，我們稱之為外顯子,，它們被無意義的片段即內(nèi)含子所分隔,。而RNA是產(chǎn)生生命必需蛋白質(zhì)的必須原材料，為了使細(xì)胞產(chǎn)生RNA,，必須精確地移除無意義的內(nèi)含子,，并連接有意義的外顯子，這個過程叫作剪接,。
在我們復(fù)雜而混亂的遺傳編碼中,，細(xì)胞區(qū)分有用片段和垃圾片段的機(jī)制，是一個基本的生物學(xué)問題?，F(xiàn)在,，以色列拉特維夫大學(xué)Sackler醫(yī)學(xué)院的Gil Ast教授和他的學(xué)生已經(jīng)成功的解決了這個問題。
這項開創(chuàng)性的研究結(jié)果發(fā)表在最近一期的Nature Structural and Molecular Biology上,，研究表明,，一個新的機(jī)制能夠解釋剪接的工作原理,。這項發(fā)現(xiàn)將使我們能夠更加深入的了解包囊纖維化，癌癥（特定）這類疾病,。
Ast教授解釋說,，他們已經(jīng)獲得了一些新發(fā)現(xiàn)。在DNA水平,，外顯子和內(nèi)含子的包裝是不一樣的,。這是一項意義重大的發(fā)現(xiàn)，告訴我們基因表達(dá)過程的發(fā)生比我們先前認(rèn)為的更早,。這將給我們提供新的發(fā)現(xiàn)和診斷疾病的線索,。
對于癌癥，在癌癥干細(xì)胞中,，DNA的結(jié)構(gòu)就與非癌癥細(xì)胞不一樣,，這些結(jié)構(gòu)可能改變RNA“編輯”的方式，導(dǎo)致外顯子不一樣的連接,，因此就產(chǎn)生不同的蛋白,。目前，Ast的研究團(tuán)隊正在利用這項發(fā)現(xiàn)探索新的藥物,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Structural & Molecular Biology 16, 990 - 995 (2009) 16 August 2009 | doi:10.1038/nsmb.1659
Chromatin organization marks exon-intron structure
Schraga Schwartz1, Eran Meshorer2 & Gil Ast1
An increasing body of evidence indicates that transcription and splicing are coupled, and it is accepted that chromatin organization regulates transcription. Little is known about the cross-talk between chromatin structure and exon-intron architecture. By analysis of genome-wide nucleosome-positioning data sets from humans, flies and worms, we found that exons show increased nucleosome-occupancy levels with respect to introns, a finding that we link to differential GC content and nucleosome-disfavoring elements between exons and introns. Analysis of genome-wide chromatin immunoprecipitation data in humans and mice revealed four specific post-translational histone modifications enriched in exons. Our findings indicate that previously described enrichment of H3K36me3 modifications in exons reflects a more fundamental phenomenon, namely increased nucleosome occupancy along exons. Our results suggest an RNA polymerase II–mediated cross-talk between chromatin structure and exon-intron architecture, implying that exon selection may be modulated by chromatin structure.
1 Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.
2 Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem, Israel.
