美國北卡羅來納大學的科學家發(fā)現(xiàn),，F(xiàn)LASH蛋白在DNA復制過程中起著重要的作用。這項研究發(fā)表在10月23日Molecular Cell雜志上,。
之前已有研究表明,，該蛋白質(zhì)在啟動細胞凋亡(或稱細胞程序性死亡)過程中也發(fā)揮著作用。凋亡是當細胞因病毒感染或突變體積累所導致的細胞損傷無法修復時,，在基因調(diào)控下,，失去作用或受損的細胞發(fā)生自我毀滅。凋亡在胚胎發(fā)育中也至關重要,，細胞選擇性的死亡使得干細胞能夠分化成不同身體結(jié)構(gòu),，如手指和腳趾等。
據(jù)該報告作者Zbigniew Dominsk介紹，該研究證實了FLASH蛋白是組蛋白信使RNA（負責表達組蛋白的RNA）合成過程中所必需的蛋白質(zhì),。這也是研究人員首次發(fā)現(xiàn)組蛋白信使RNA與細胞凋亡之間的潛在聯(lián)系,。組蛋白是組成染色質(zhì)的主要蛋白，DNA和組蛋白在細胞內(nèi)的代謝信號作用下相互作用,，F(xiàn)LASH蛋白起著調(diào)節(jié)基因表達的作用,。
在該研究中，Dominski通過對整個試驗方法的調(diào)整,，使得在正常細胞內(nèi)才能發(fā)生的生化過程——FLASH蛋白調(diào)節(jié)組蛋白信使RNA成熟的過程——轉(zhuǎn)移到試管中進行研究,。該方法使研究人員準確找出FLASH蛋白中與形成組蛋白信使RNA相關的約100個氨基酸。而該蛋白質(zhì)復合體剩余部分的2,000多個氨基酸,，研究人員猜測,，可能負責控制細胞內(nèi)其它的生化過程，如細胞凋亡或DNA復制等,。（生物谷Bioon.com）
生物谷推薦原始出處：
Molecular Cell, 23 October 2009 doi:10.1016/j.molcel.2009.08.016
FLASH, a Proapoptotic Protein Involved in Activation of Caspase-8, Is Essential for 3′ End Processing of Histone Pre-mRNAs
Xiao-cui Yang1, Brandon D. Burch2, Yan Yan1, William F. Marzluff1 and Zbigniew Dominski1, ,
1 Department of Biochemistry and Biophysics and Program in Molecular Biology and Biotechnology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
2 Curriculum in Genetics and Molecular Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3′ end processing of histone pre-mRNA requires U7 snRNP, which binds downstream of the cleavage site and recruits the endonuclease CPSF-73. U7 snRNP contains a unique Sm ring in which the canonical SmD2 protein is replaced by Lsm11. We used the yeast two-hybrid system to identify binding partners of Lsm11 and selected the proapoptotic protein FLASH. Human FLASH interacts with Lsm11 in vitro and stimulates 3′ end processing of histone pre-mRNA in mammalian nuclear extracts. We also identified the FLASH ortholog in Drosophila and demonstrate that it interacts with Lsm11 in vitro and in vivo. Drosophila FLASH localizes to histone locus bodies, and its depletion from fly cells inhibits U7-dependent processing, resulting in polyadenylation of histone mRNAs. These results demonstrate that FLASH is an essential factor required for 3′ end maturation of histone mRNAs in both vertebrates and invertebrates and suggest a potential link between this process and apoptosis.
