Loyer Pascal, Trembley Janeen H, Katona Robert, Kidd Vincent J, Lahti Jill M
Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
Cell Signal. 2005 Sep;17(9):1033-51. doi: 10.1016/j.cellsig.2005.02.005.
The production of mRNAs in all living organisms is an extremely complex process that includes multiple catalytic activities such as transcription, capping, splicing, polyadenylation, cleavage and export. All of these processes are controlled by a large group of proteins which form very dynamic complexes interacting with DNA and pre-mRNAs to coordinate these activities. Phosphorylations play a central role in regulating formation, activation and inactivation of these complexes. A growing number of protein kinases have been identified that are capable of phosphorylating proteins involved in mRNA production. Among them, Cyclin-dependent Kinases (CDKs) represent a family of serine/threonine protein kinases that become active upon binding to a cyclin regulatory partner. CDK/cyclin complexes were first identified as crucial regulators of cell cycle progression. More recently, CDK/cyclin complexes have also been implicated in transcription and mRNA processing leading to the concept of an intricate network of CDK/cyclin complexes regulating cell cycle, transcription and mRNA processing via cross-talk between multiple CDKs. In this review, we discuss the role of CDK/cyclin-dependent phosphorylation in the regulation of transcription and RNA splicing and highlight recent findings that indicate the involvement of CDK/cyclin complexes in connecting transcription and RNA splicing.
所有生物体中mRNA的产生是一个极其复杂的过程,包括多种催化活性,如转录、加帽、剪接、聚腺苷酸化、切割和输出。所有这些过程都由一大组蛋白质控制,这些蛋白质形成非常动态的复合物,与DNA和前体mRNA相互作用以协调这些活动。磷酸化在调节这些复合物的形成、激活和失活中起着核心作用。越来越多的蛋白激酶已被鉴定出来,它们能够磷酸化参与mRNA产生的蛋白质。其中,细胞周期蛋白依赖性激酶(CDK)代表一类丝氨酸/苏氨酸蛋白激酶,它们在与细胞周期蛋白调节伴侣结合后变得活跃。CDK/细胞周期蛋白复合物最初被鉴定为细胞周期进程的关键调节因子。最近,CDK/细胞周期蛋白复合物也与转录和mRNA加工有关,从而产生了一个复杂的CDK/细胞周期蛋白复合物网络的概念,该网络通过多个CDK之间的相互作用调节细胞周期、转录和mRNA加工。在这篇综述中,我们讨论了CDK/细胞周期蛋白依赖性磷酸化在转录和RNA剪接调节中的作用,并强调了最近的发现,这些发现表明CDK/细胞周期蛋白复合物参与连接转录和RNA剪接。