cotranscriptional

Cotranscriptional describes processes that occur on a nascent RNA while transcription by RNA polymerase proceeds. In eukaryotes, many RNA maturation steps begin during transcription, allowing rapid and coordinated gene expression. While prokaryotes often exhibit tight transcription-translation coupling, cotranscriptional RNA processing is particularly prominent in eukaryotic nuclei, where RNA maturation steps are integrated with transcription.

Key cotranscriptional processes include 5' capping of the nascent transcript, early recruitment of RNA processing factors, splicing of introns, and 3' end formation and polyadenylation. RNA editing, RNA folding, and quality control checks can also occur cotranscriptionally. The spatial and temporal coupling of these events helps ensure proper mRNA structure, stability, and export readiness, and it can influence alternative splicing outcomes and gene expression levels.

Mechanistically, the C-terminal domain (CTD) of RNA polymerase II serves as a dynamic platform that recruits and coordinates processing factors as elongation proceeds. Chromatin structure and transcription elongation rate modulate processing decisions; for example, slower elongation can promote inclusion of alternative exons. Cotranscriptional events are therefore sensitive to regulatory cues, chromatin state, and RNA polymerase II dynamics.

Techniques such as native elongating transcript sequencing (NET-seq) and chromatin-associated RNA sequencing enable the study of nascent transcripts and cotranscriptional processing in vivo. Understanding cotranscriptional coupling provides insight into gene expression control and how processing errors can contribute to disease.