Hluchý Milan, Blazek Dalibor
Central European Institute of Technology (CEITEC), Masaryk University, 62500 Brno, Czech Republic.
Central European Institute of Technology (CEITEC), Masaryk University, 62500 Brno, Czech Republic.
Trends Cell Biol. 2024 Sep 7. doi: 10.1016/j.tcb.2024.08.004.
The ability of a cell to properly express its genes depends on optimal transcription and splicing. RNA polymerase II (RNAPII) transcribes protein-coding genes and produces pre-mRNAs, which undergo, largely co-transcriptionally, intron excision by the spliceosome complex. Spliceosome activation is a major control step, leading to a catalytically active complex. Recent work has showed that cyclin-dependent kinase (CDK)11 regulates spliceosome activation via the phosphorylation of SF3B1, a core spliceosome component. Thus, CDK11 arises as a major coordinator of gene expression in metazoans due to its role in the rate-limiting step of pre-mRNA splicing. This review outlines the evolution of CDK11 and SF3B1 and their emerging roles in splicing regulation. It also discusses how CDK11 and its inhibition affect transcription and cell cycle progression.
细胞正确表达其基因的能力取决于最佳转录和剪接。RNA聚合酶II(RNAPII)转录蛋白质编码基因并产生前体mRNA,前体mRNA在很大程度上在转录过程中由剪接体复合物进行内含子切除。剪接体激活是一个主要的控制步骤,会产生具有催化活性的复合物。最近的研究表明,细胞周期蛋白依赖性激酶(CDK)11通过剪接体核心组分SF3B1的磷酸化来调节剪接体激活。因此,由于CDK11在前体mRNA剪接的限速步骤中发挥作用,它成为后生动物基因表达的主要协调者。本综述概述了CDK11和SF3B1的进化及其在剪接调控中的新作用。它还讨论了CDK11及其抑制如何影响转录和细胞周期进程。