Mechanisms of transcription termination across the coding and noncoding loci of the genome.

Abstract

Transcription termination by RNA polymerase II (Pol II) defines transcriptional boundaries of protein-coding and noncoding transcription units throughout the genome. Rather than being a passive endpoint of elongation, termination is a tightly regulated and context-dependent process that shapes gene expression, RNA surveillance pathways and chromatin environments. This Review summarizes mechanistic and conceptual aspects of Pol II termination, focusing primarily on studies in metazoans and incorporating insights from yeast where relevant. We discuss the major termination pathways operating across different genomic contexts, including canonical cleavage and polyadenylation-dependent termination at 3' ends of genes, promoter-proximal termination mediated by the Integrator-PP2A complex (INTAC), Pol II turnover via the E3 ligase CRL3^ARMC5 and cap-dependent RNA surveillance. We further examine how termination restrains pervasive transcription and how its dysregulation compromises genome stability, particularly through the accumulation of R-loops. Finally, we discuss how termination interfaces with RNA processing, export and nuclear decay pathways to guide RNA fate decisions.