Functional integration of transcriptional and RNA processing machineries

Abstract

Cotranscriptional RNA processing not only permits temporal RNA processing before the completion of transcription but also allows sequential recognition of RNA processing signals on nascent transcripts threading out from the elongating RNA polymerase II (RNAPII) complex. Rapid progress in recent years has established multiple contacts that physically connect the transcription and RNA processing machineries, which centers on the C-terminal domain (CTD) of the largest subunit of RNAPII. Although cotranscriptional RNA processing has been substantiated, the evidence for 'reciprocal' coupling starts to emerge, which emphasizes functional integration of transcription and RNA processing machineries in a mutually beneficial manner for efficient and regulated gene expression.

Figure 1

Coupling between transcription and pre-mRNA processing. The RNA polymerase II (RNAPII) is modified on its CTD with Ser5 phosphorylation predominately at the beginning of the gene (blue line) and Ser2 phosphorylation in the middle and end of the gene (yellow line). 5′ capping enzymes are recruited through direct interactions with Ser5 phosphorylated CTD to catalyze the co-transcriptional capping reaction. Various splicing factors are recruited during the elongation phase of transcription, most of which in a CTD Ser2 phosphorylation dependent manner, to facilitate co-transcriptional splicing. The 3′ end formation is functionally tied to transcription termination. Importantly, increasing evidence now suggests that the transcription and RNA processing machineries are functionally integrated in a reciprocal fashion such that individual co-transcriptional processing events also influence transcription at different phases.