Featured article in Nature Reviews

In March, a review written by senior postdoc Iris Jonkers and John Lis (Cornell University, NY) was the featured article in a special issue on transcription, Nature Reviews Molecular Cell Biology

Getting up to speed with transcription elongation by RNA polymerase II
Iris Jonkers & John T Lis
Nature Reviews Molecular Cell Biology 2015;16:167-177, doi:10.1038/nrm3953
Published online 18 February 2015

"Transcription is the primary control point for gene expression. It therefore determines cellular function and cell identity, and must be tightly regulated to achieve a high degree of specificity. Thus, it is not surprising that transcription is subject to regulation at each of its steps — initiation, elongation and termination. Many proteins, RNAs and features of chromatin are involved in these regulatory steps to ensure that, in each cell, the transcriptional machinery is recruited and activated at specific genes, progresses through chromatin at appropriate rates, and terminates in a controlled manner.

This specially commissioned Focus issue highlights the exquisite complexity of transcription regulation. Recent structural information on RNA polymerase II (Pol II) initiation complexes provides insight into the mechanisms by which Pol II binds specific promoters and initiates RNA synthesis. At the genome-wide level, we now have a better understanding of how the selective activation of enhancers drives cell-specific gene expression, how promoter-proximal pausing of Pol II and transcription elongation rates affect gene expression and co-transcriptional processes, and how transcription termination pathways contribute to shaping the transcriptome. Insights have also been gained into the mechanisms that enable transcription-associated histone exchange and chromatin remodelling and into the important functions of the Mediator complex in the regulation of enhancer–promoter gene looping, transcription initiation and elongation." Issue contents

Abstract | Recent advances in sequencing techniques that measure nascent transcripts and that reveal the positioning of RNA polymerase II (Pol II) have shown that the pausing of Pol II in promoter-proximal regions and its release to initiate a phase of productive elongation are key steps in transcription regulation. Moreover, after the release of Pol II from the promoter-proximal region, elongation rates are highly dynamic throughout the transcription of a gene, and vary on a gene‑by‑gene basis. Interestingly, Pol II elongation rates affect co-transcriptional processes such as splicing, termination and genome stability. Increasing numbers of factors and regulatory mechanisms have been associated with the steps of transcription elongation by Pol II, revealing that elongation is a highly complex process. Elongation is thus now recognized as a key phase in the regulation of transcription by Pol II. more