Mechanisms of RNA Polymerase II Termination at the 3'-End of Genes

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.