title: The point of no return: The poly(A)-associated elongation checkpoint.
abstract: Cyclin-dependent kinases play critical roles in transcription by RNA polymerase II (pol II) and processing of the transcripts. For example, CDK9 regulates transcription of protein-coding genes, splicing, and 3' end formation of the transcripts. Accordingly, CDK9 inhibitors have a drastic effect on the production of mRNA in human cells. Recent analyses indicate that CDK9 regulates transcription at the early-elongation checkpoint of the vast majority of pol II-transcribed genes. Our recent discovery of an additional CDK9-regulated elongation checkpoint close to poly(A) sites adds a new layer to the control of transcription by this critical cellular kinase. This novel poly(A)-associated checkpoint has the potential to powerfully regulate gene expression just before a functional polyadenylated mRNA is produced: the point of no return. However, many questions remain to be answered before the role of this checkpoint becomes clear. Here we speculate on the possible biological significance of this novel mechanism of gene regulation and the players that may be involved.
authors: a Sir William Dunn School of Pathology, University of Oxford , Oxford OX1 3RE , UK.
authors: Michael
authors: M
authors: Tellier
authors: a Sir William Dunn School of Pathology, University of Oxford , Oxford OX1 3RE , UK.
authors: Ivan
authors: I
authors: Ferrer-Vicens
authors: a Sir William Dunn School of Pathology, University of Oxford , Oxford OX1 3RE , UK.
authors: Shona
authors: S
authors: Murphy
mesh_terms: D059447:Cell Cycle Checkpoints; D042863:Cyclin-Dependent Kinase 9 / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D026723:Polyadenylation; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D061805:Transcription Elongation, Genetic
chemical_list: D012333:RNA, Messenger; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9; D012319:RNA Polymerase II
keywords: Elongation; P-TEFb; elongation checkpoint; pol II; polyadenylation