Shilatifard A
Saint Louis University School of Medicine, Edward A. Doisy Department of Biochemistry and Molecular Biology, MO 63104, USA.
Biol Chem. 1998 Jan;379(1):27-31. doi: 10.1515/bchm.1998.379.1.27.
Eukaryotic messenger RNA (mRNA) synthesis is a complex multi-stage process that requires the concerted action of many cellular factors to generate a mature functional message. This elaborate process by RNA polymerase II (pol II) proceeds via multiple stages-preinitiation, initiation (Figure 1), promoter clearance, elongation (Figure 1) and termination - which have come to be referred to collectively as the transcription cycle. Although the preinitiation and initiation stages of transcription have received the most attention during the past decade, the past few years have been a watershed for biochemical studies of the pol II elongation complex. Recent studies have demonstrated the existence of several families of pol II elongation factors and nuclear proteins that can govern the activity of pol II during mRNA chain elongation. New findings have revealed that the elongation stage of transcription is a critical site for the regulation of gene expression. Evidence obtained to date suggests that eukaryotes regulate elongation by both 'general' and 'activator dependent' mechanisms. These mechanisms necessitate alteration of pol II's catalytic site, modification of chromatin structure, phosphorylation of the pol II carboxyl-terminal domain (CTD) and involvement of other components of the transcription machinery to increase the rate and efficiency of transcription elongation. This minireview is an annotation on the recent progress in studies of the biochemical mechanism and molecular regulation of the elongation stages of eukaryotic mRNA synthesis. The recent developments that have guided our understanding and propelled current research on transcription elongation by mammalian pol II will be described here.
真核生物信使核糖核酸(mRNA)的合成是一个复杂的多阶段过程,需要许多细胞因子协同作用才能产生成熟的功能性信息。RNA聚合酶II(pol II)进行的这一精细过程通过多个阶段进行——起始前、起始(图1)、启动子清除、延伸(图1)和终止——这些阶段统称为转录循环。尽管在过去十年中转录的起始前和起始阶段受到了最多关注,但过去几年对于pol II延伸复合物的生化研究来说是一个分水岭。最近的研究表明存在几个pol II延伸因子家族和核蛋白家族,它们可以在mRNA链延伸过程中调控pol II的活性。新的发现揭示转录的延伸阶段是基因表达调控的关键位点。迄今为止获得的证据表明,真核生物通过“一般”和“激活因子依赖”机制来调控延伸。这些机制需要改变pol II的催化位点、修饰染色质结构、磷酸化pol II的羧基末端结构域(CTD)以及转录机制的其他组分参与,以提高转录延伸的速率和效率。本综述是对真核生物mRNA合成延伸阶段生化机制和分子调控研究最新进展的注释。这里将描述引导我们理解并推动当前对哺乳动物pol II转录延伸研究的最新进展。