The transcription cycle in eukaryotes: From productive initiation to RNA polymerase II recycling

The cycle of eukaryotic transcription, from initiation to elongation and termination is regulated at multiple steps. Coordinated action of regulatory factors keeps in check the transcriptional competence of RNA polymerase II (RNAPII) at different stages. Productive transcription requires the escape of the paused RNAPII from the promoter and transition to rapid elongation of the transcript. Numerous studies have identified diverse mechanisms of initiating transcription by overriding inhibitory signals at the gene promoter. The general theme that has emerged is that the balance between positive and negative regulatory factors determines the overall rate of transcription. Recently transcription termination has emerged as an important area of transcriptional regulation that is coupled with the efficient recycling of RNAPII. The factors associated with transcription termination can also mediate gene looping and thereby determine the efficiency of re-initiation. This review highlights these regulatory steps, the key modulators involved in transcription dynamics, and the emerging tools to analyze them.

► Eukaryotic transcription is a highly coordinated and stringently regulated event.
► Multiple rounds of initiation–elongation–termination occur in a cyclic pattern.
► Alleviation of pausing by diverse mechanisms stimulates the transcription process.
► Gene looping facilitates RNA polymerase II recycling via promoter–terminator contact.
► A new dimension in transcriptional regulation is revealed by single molecule studies.