RNA polymerase II speed: a key player in controlling and adapting transcriptome composition

RNA polymerase II (RNA Pol II) speed or elongation rate, i.e., the number of nucleotides synthesized per unit of time, is a major determinant of transcriptome composition. It controls co‐transcriptional processes such as splicing, polyadenylation, and transcription termination, thus regulating the production of alternative splice variants, circular RNAs, alternatively polyadenylated transcripts, or read‐through transcripts. RNA Pol II speed itself is regulated in response to intra‐ and extra‐cellular stimuli and can in turn affect the transcriptome composition in response to these stimuli. Evidence points to a potentially important role of transcriptome composition modification through RNA Pol II speed regulation for adaptation of cells to a changing environment, thus pointing to a function of RNA Pol II speed regulation in cellular physiology. Analyzing RNA Pol II speed dynamics may therefore be central to fully understand the regulation of physiological processes, such as the development of multicellular organisms. Recent findings also raise the possibility that RNA Pol II speed deregulation can be detrimental and participate in disease progression. Here, we review initial and current approaches to measure RNA Pol II speed, as well as providing an overview of the factors controlling speed and the co‐transcriptional processes which are affected. Finally, we discuss the role of RNA Pol II speed regulation in cell physiology. Graphical Abstract This review discusses recent advances in understanding the regulation and functional effects of RNA polymerase II speed, as well as approaches for its experimental assessment.