總所周知,,一部電影包含數千個隨機的場景,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含子所分隔,。而RNA是產生生命必需蛋白質的必須原材料,,為了使細胞產生RNA,必須精確地移除無意義的內含子,,并連接有意義的外顯子,,這個過程叫作剪接。
在我們復雜而混亂的遺傳編碼中,,細胞區(qū)分有用片段和垃圾片段的機制,,是一個基本的生物學問題?,F在,以色列拉特維夫大學Sackler醫(yī)學院的Gil Ast教授和他的學生已經成功的解決了這個問題,。
這項開創(chuàng)性的研究結果發(fā)表在最近一期的Nature Structural and Molecular Biology上,,研究表明,一個新的機制能夠解釋剪接的工作原理,。這項發(fā)現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,,他們已經獲得了一些新發(fā)現,。在DNA水平,外顯子和內含子的包裝是不一樣的,。這是一項意義重大的發(fā)現,,告訴我們基因表達過程的發(fā)生比我們先前認為的更早。這將給我們提供新的發(fā)現和診斷疾病的線索,。
對于癌癥,,在癌癥干細胞中,DNA的結構就與非癌癥細胞不一樣,,這些結構可能改變RNA“編輯”的方式,,導致外顯子不一樣的連接,因此就產生不同的蛋白,。目前,,Ast的研究團隊正在利用這項發(fā)現探索新的藥物。(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.