早期延伸复合物的形成
中文名称
通路描述
RNA 聚合酶 II（RNAPII）的转录延伸受多种转录延伸因子（trans-acting）以及顺式作用元件的控制。转录延伸是产生正确 mRNA 的关键限速步骤，其中 Pol II CTD 的磷酸化是一个关键的生化事件。蛋白激酶抑制剂如 5,6-二氯 -1- 环戊烯基苯并咪唑（DRB）会严重损害 Pol II 转录中 CTD 磷酸化的作用，并诱导延伸中的 Pol II 停滞。DRB 敏感的 Pol II CTD 在延伸期间被激活，使得分离出两个因子组成为可能：负延伸因子（NELF）和 DRB 敏感性诱导因子（DSIF）。P-Tefb 是一种 DRB 敏感的、由 Cdk9 组成的细胞周期依赖性 CTD 激酶，负责在延伸期间对 Pol II CTD 进行丝氨酸 -2 磷酸化。DSIF、NELF 和 P-TEFb 如何在 Pol II 调控的延伸中协同作用，其机制尚未完全阐明。各种生化证据表明，DSIF 和 NELF 通过与含有低磷酸化 CTD 的聚合酶相互作用来负向调控延伸。随后，由 P-Tefb 对 Pol II CTD 的磷酸化可能会通过抑制 DSIF 和 NELF 与延伸复合物的相互作用来促进延伸。
英文描述
Formation of the Early Elongation Complex Transcription elongation by RNA polymerase II (RNAPII) is controlled by a number of trans-acting transcription elongation factors as well as by cis-acting elements. Transcription elongation is a rate-limiting step for proper mRNA production in which the phosphorylation of Pol II CTD is a crucial biochemical event. The role of CTD phosphorylation in transcription by Pol II is greatly impaired by protein kinase inhibitors such as 5,6-dichloro-1- ribofuranosylbenzimidazole (DRB), which block CTD phosphorylation and induce arrest of elongating Pol II. DRB-sensitive activation Pol II CTD during elongation has enabled the isolation of two sets of factors -Negative Elongation Factors (NELF) and DRB sensitivity inducing factor (DSIF). P-Tefb is a DRB-sensitive, cyclin-dependent CTD kinase composed of Cdk9 that carries out Serine-2 phosphorylation of Pol II CTD during elongation.The mechanism by which DSIF, NELF and P-TEFb act together in Pol II-regulated elongation is yet to be fully understood. Various biochemical evidences point to a model in which DSIF and NELF negatively regulate elongation through interactions with polymerase containing a hypophosphorylated CTD. Subsequent phosphorylation of the Pol II CTD by P-Tefb might promote elongation by inhibiting interactions of DSIF and NELF with the elongation complex.
所含基因
32 个基因