美国北卡罗来纳大学的科学家发现,FLASH蛋白在DNA复制过程中起着重要的作用。这项研究发表在10月23日Molecular Cell杂志上。
之前已有研究表明,该蛋白质在启动细胞凋亡(或称细胞程序性死亡)过程中也发挥着作用。凋亡是当细胞因病毒感染或突变体积累所导致的细胞损伤无法修复时,在基因调控下,失去作用或受损的细胞发生自我毁灭。凋亡在胚胎发育中也至关重要,细胞选择性的死亡使得干细胞能够分化成不同身体结构,如手指和脚趾等。
据该报告作者Zbigniew Dominsk介绍,该研究证实了FLASH蛋白是组蛋白信使RNA(负责表达组蛋白的RNA)合成过程中所必需的蛋白质。这也是研究人员首次发现组蛋白信使RNA与细胞凋亡之间的潜在联系。组蛋白是组成染色质的主要蛋白,DNA和组蛋白在细胞内的代谢信号作用下相互作用,FLASH蛋白起着调节基因表达的作用。
在该研究中,Dominski通过对整个试验方法的调整,使得在正常细胞内才能发生的生化过程——FLASH蛋白调节组蛋白信使RNA成熟的过程——转移到试管中进行研究。该方法使研究人员准确找出FLASH蛋白中与形成组蛋白信使RNA相关的约100个氨基酸。而该蛋白质复合体剩余部分的2,000多个氨基酸,研究人员猜测,可能负责控制细胞内其它的生化过程,如细胞凋亡或DNA复制等。(生物谷Bioon.com)
生物谷推荐原始出处:
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.