含有連續(xù)鳥嘌呤堿基的核苷酸能夠形成G-四鏈體結(jié)構(gòu),，傾向形成G-四鏈體結(jié)構(gòu)的序列(PQS)廣泛分布在原核生物和真核生物的基因組中,，G-四鏈體結(jié)構(gòu)參與一些重要的生理和病理過程,，如DNA的復(fù)制,，轉(zhuǎn)錄和癌癥的發(fā)生等,。然而對(duì)于G-四鏈體結(jié)構(gòu)如何在基因組中產(chǎn)生這一問題仍然不清楚,。
中科院動(dòng)物研究所端粒與衰老研究組最近的研究發(fā)現(xiàn)，雙鏈DNA轉(zhuǎn)錄過程中在RNA聚合酶后方形成的負(fù)超螺旋能夠誘導(dǎo)產(chǎn)生G-四鏈體結(jié)構(gòu),。進(jìn)一步的結(jié)果表明,，轉(zhuǎn)錄誘導(dǎo)G-四鏈體的產(chǎn)生可以有效地在遠(yuǎn)離轉(zhuǎn)錄起始位點(diǎn)數(shù)千堿基的地方發(fā)生，同時(shí)改變上游地區(qū)蛋白質(zhì)對(duì)DNA的識(shí)別和相互作用,。這一特性提示基因組DNA雙鏈中下游基因的轉(zhuǎn)錄能夠遠(yuǎn)距離地影響和調(diào)節(jié)上游DNA的結(jié)構(gòu)和相關(guān)的生物學(xué)功能,。或者說,，能夠形成G-四鏈體結(jié)構(gòu)的序列作為感應(yīng)元件能夠遠(yuǎn)距離感應(yīng)下游轉(zhuǎn)錄事件的發(fā)生,，所形成的G-四鏈體結(jié)構(gòu)進(jìn)一步作為調(diào)控元件調(diào)控基因的轉(zhuǎn)錄或其它生理活動(dòng)。與這一特性相對(duì)應(yīng),，該研究利用生物信息學(xué)的方法,，發(fā)現(xiàn)恒溫動(dòng)物中能夠形成G-四鏈體結(jié)構(gòu)的序列富集在基因的上游,，但是在基因的下游幾乎不存在富集現(xiàn)象。它表明這些功能為進(jìn)化所選擇,。
該項(xiàng)研究成果于5月28日在線發(fā)表在Nucleic Acids Research上，并被推薦到Faculty of 1000,。
該論文的通訊作者是譚錚研究員,，第一作者是博士研究生張超。
該項(xiàng)研究工作得到科技部“973”國家重點(diǎn)項(xiàng)目,、國家自然科學(xué)基金的資助,。(生物谷Bioon.com)
相關(guān)閱讀
童坦君院士、譚錚研究員：端粒研究方興未艾
生物谷推薦英文摘要
Nucl. Acids Res. doi: 10.1093/nar/gkt443
DNA G-quadruplex formation in response to remote downstream transcription activity: long-range sensing and signal transducing in DNA double helix
G-quadruplexes, four-stranded structures formed by Guanine-rich nucleic acids, are implicated in many physiological and pathological processes. G-quadruplex-forming sequences are abundant in genomic DNA, and G-quadruplexes have recently been shown to exist in the genome of mammalian cells. However, how G-quadruplexes are formed in the genomes remains largely unclear. Here, we show that G-quadruplex formation can be remotely induced by downstream transcription events that are thousands of base pairs away. The induced G-quadruplexes alter protein recognition and cause transcription termination at the local region. These results suggest that a G-quadruplex-forming sequence can serve as a sensor or receiver to sense remote DNA tracking activity in response to the propagation of mechanical torsion in a DNA double helix. We propose that the G-quadruplex formation may provide a mean for long-range sensing and communication between distal genomic locations to coordinate regulatory transactions in genomic DNA.
