Zhao J, Hyman L, Moore C
Department of Molecular Biology and Microbiology, School of Medicine, Tufts University, Boston, Massachusetts 02111, USA.
Microbiol Mol Biol Rev. 1999 Jun;63(2):405-45. doi: 10.1128/MMBR.63.2.405-445.1999.
Formation of mRNA 3' ends in eukaryotes requires the interaction of transacting factors with cis-acting signal elements on the RNA precursor by two distinct mechanisms, one for the cleavage of most replication-dependent histone transcripts and the other for cleavage and polyadenylation of the majority of eukaryotic mRNAs. Most of the basic factors have now been identified, as well as some of the key protein-protein and RNA-protein interactions. This processing can be regulated by changing the levels or activity of basic factors or by using activators and repressors, many of which are components of the splicing machinery. These regulatory mechanisms act during differentiation, progression through the cell cycle, or viral infections. Recent findings suggest that the association of cleavage/polyadenylation factors with the transcriptional complex via the carboxyl-terminal domain of the RNA polymerase II (Pol II) large subunit is the means by which the cell restricts polyadenylation to Pol II transcripts. The processing of 3' ends is also important for transcription termination downstream of cleavage sites and for assembly of an export-competent mRNA. The progress of the last few years points to a remarkable coordination and cooperativity in the steps leading to the appearance of translatable mRNA in the cytoplasm.
真核生物中mRNA 3'末端的形成需要反式作用因子通过两种不同机制与RNA前体上的顺式作用信号元件相互作用,一种机制用于大多数依赖复制的组蛋白转录本的切割,另一种机制用于大多数真核生物mRNA的切割和多聚腺苷酸化。现在已经鉴定出了大多数基本因子,以及一些关键的蛋白质-蛋白质和RNA-蛋白质相互作用。这种加工过程可以通过改变基本因子的水平或活性,或者通过使用激活剂和抑制剂来调节,其中许多是剪接机制的组成部分。这些调节机制在细胞分化、细胞周期进程或病毒感染过程中发挥作用。最近的研究结果表明,切割/多聚腺苷酸化因子通过RNA聚合酶II(Pol II)大亚基的羧基末端结构域与转录复合物的结合,是细胞将多聚腺苷酸化限制在Pol II转录本上的方式。3'末端的加工对于切割位点下游的转录终止以及组装具有输出能力的mRNA也很重要。过去几年的研究进展表明,在导致细胞质中出现可翻译mRNA的步骤中存在着显著的协调和协同作用。