RNA聚合酶II(RNAPII)负责合成一组不同的RNA分子,包括蛋白质编码信使RNA(mRNAs)和许多短非编码RNA(ncRNAs)。为此,RNAPII依赖于多种调节转录周期的因子,从起始和启动子近端暂停,通过伸长和最终终止。基因末端的RNAPII转录终止确保了RNAPII从DNA模板中的释放及其有效的再循环用于进一步的转录循环。RNAPII的终止与3'端mRNA加工紧密偶联,这构成了后续转录终止事件的重要触发因素。在这次审查中,我们讨论了目前对RNAPII终止机制的理解,专注于基因3端的“规范”终止。我们还将变构和鱼雷模型整合到一个统一的终止模型中,并描述迄今为止已经确定的不同终止因素,在分子水平上特别关注人为因素及其作用机制。的确,近年来,结构生物学新方法的发展,生物化学和细胞生物学共同导致了对RNAPII终止的不同机制的更详细的理解,更好地理解它们在调节基因表达中的重要性,特别是在细胞压力和病理情况下。
RNA polymerase II (
RNAPII) is responsible for the synthesis of a diverse set of RNA molecules, including protein-coding messenger RNAs (mRNAs) and many short non-coding RNAs (ncRNAs). For this purpose,
RNAPII relies on a multitude of factors that regulate the transcription cycle, from initiation and promoter-proximal pausing, through elongation and finally termination.
RNAPII transcription termination at the end of genes ensures the release of
RNAPII from the DNA template and its efficient recycling for further rounds of transcription. Termination of
RNAPII is tightly coupled to 3\'-end mRNA processing, which constitutes an important trigger for the subsequent transcription termination event. In this review, we discuss the current understanding of
RNAPII termination mechanisms, focusing on \'canonical\' termination at the 3\'-end of genes. We also integrate the allosteric and \'torpedo\' models into a unified model of termination, and describe the different termination factors that have been identified to date, paying special attention to the human factors and their mechanism of action at the molecular level. Indeed, in recent years the development of novel approaches in structural biology, biochemistry and cell biology have together led to a more detailed comprehension of the different mechanisms of RNAPII termination, and a better understanding of their importance in regulating gene expression, especially under cellular stress and pathological situations.