Thanks to a first-of-its-kind platform, we are starting to understand how the molecular engine responsible for transcription in mammals controls its speed. A team of researchers from The Rockefeller University (NY, USA) and Fudan University Shanghai Cancer Center (Shanghai, China) has invented a novel single-molecule platform to illuminate the intricacies of mammalian DNA transcription, with far-reaching implications throughout biology, including cancer and aging research. Transcription elongation by RNA polymerase II (Pol II) – the enzyme complex responsible for transcribing DNA into mRNA in eukaryotes – is an essential part of gene expression. During this process, the speed at which the protein complex moves along the DNA template is not constant and is governed by several elongation factors. In metazoans, we know that Pol II pauses after assembling the initiation complex at the promoter and transcribing 30–60 nucleotides of RNA. At this point, elongation factors such as P-TEFb, DSIF and PAF1C initiate the release of Pol II and kickstart a period of rapid transcription, before the molecular machine slams on the breaks and decelerates toward the 3′ end of the gene to allow for the termination of transcription. Dysregulation of elongation has been linked to disease and aging; however, the exact regulatory mechanisms that underpin it remain incompletely understood, especially for higher eukaryotes. Research on the mammalian elongation complex has thus far been limited by a lack of appropriate techniques; those techniques used could not illuminate the contributions of individual proteins nor capture the complexity of eukaryotic regulatory mechanisms in single-molecule studies…
