Paused RNA Polymerase Quashes New Initiation of Transcription

Pauses may help cells fine-tune gene expression.

Oct 1, 2017
Shawna Williams

POLYMERASE INTERFERENCE: During gene expression, multiple RNA polymerase II enzymes commonly transcribe a gene simultaneously. But if a polymerase pauses on the gene, no new transcription is initiated until it restarts.
See full infographic: WEB 

The paper
W. Shao, J. Zeitlinger, “Paused RNA polymerase II inhibits new transcriptional initiation,” Nat Genet, 49:1045-51, 2017.

When it comes to regulating gene expression, transcriptional initiation tends to get a lot of attention. But it’s become clear in the past decade that RNA polymerase II, the enzyme that transcribes DNA to RNA, frequently pauses after reading just a few dozen base pairs. This break surely affects gene expression rates—though its impact has not been obvious. Julia Zeitlinger and graduate student Wanqing Shao of the Stowers Institute for Medical Research in Kansas City, Missouri, recently found that as long as RNA polymerase remains stalled, very little new transcription is initiated.

Zeitlinger and Shao came to this conclusion by using a drug to freeze RNA polymerase II and transcription factors in place in Drosophila cells, then analyzing the positions of polymerases throughout the genome with a technique called ChIP-nexus. “We could clearly see minimal initiation in the presence of paused polymerase,” she says. The result was initially surprising, she adds, because it’s been shown that promoters with a strong propensity for downstream polymerase-pausing are associated with faster gene expression in response to a developmental signal.

“I think that the idea of having one rate-limiting step is sort of appealing, and a lot of biologists sort of intuitively think that way,” she says. “But it’s actually not a good way to design a system . . . because it makes it more stochastic, more random.” It makes sense that there would be a system in place to ensure transcription isn’t simultaneously paused and initiated on the same gene, she says, but the mechanics of how the paused polymerase wards off new initiation remain to be elucidated.

Craig Kaplan, a molecular biologist at Texas A&M University, says this and other recent studies also make it clear that pausing can occur for very different lengths of time depending on the promoter. This helps give cells a “buffet of choices in how expression may happen,” he notes. “The regulation doesn’t have to be thought of as on or off; it may be how frequently you make a transcript, or whether you’re making your transcript in bursts, or whether you’re making transcripts evenly.”

But Patrick Cramer of the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, wants to see the results confirmed by other studies. “Occupancy changes are certainly an indication for changes in kinetics, but are not a proof, because occupancy can change either because the number of factors bound to DNA changes or because their residency time on DNA changes, or both,” he writes in an email to The Scientist.

“Transcription is an old field, and I think it’s often seen as, ‘Oh, it’s so well studied,’” says Zeitlinger. “[But] there are a lot of things we don’t understand. . . . There are so many open questions in the field that are quite fundamental.”

January 2019

Cannabis on Board

Research suggests ill effects of cannabinoids in the womb


Sponsored Product Updates

FORMULATRIX® digital PCR technology to be acquired by QIAGEN
FORMULATRIX® digital PCR technology to be acquired by QIAGEN
FORMULATRIX has announced that their digital PCR assets, including the CONSTELLATION® series of instruments, is being acquired by QIAGEN N.V. (NYSE: QGEN, Frankfurt Stock Exchange: QIA) for up to $260 million ($125 million upfront payment and $135 million of milestones).  QIAGEN has announced plans for a global launch in 2020 of a new series of digital PCR platforms that utilize the advanced dPCR technology developed by FORMULATRIX combined with QIAGEN’s expertise in assay development and automation.
Application of CRISPR/Cas to the Generation of Genetically Engineered Mice
Application of CRISPR/Cas to the Generation of Genetically Engineered Mice
With this application note from Taconic, learn about the power that the CRISPR/Cas system has to revolutionize the field of custom mouse model generation!
Translational Models of Obesity, Dysmetabolism, Diabetes, and Complications
Translational Models of Obesity, Dysmetabolism, Diabetes, and Complications
This webinar, from Crown Bioscience, presents a unique continuum of translational dysmetabolic platforms that more closely mimic human disease. Learn about using next-generation rodent and spontaneously diabetic non-human primate models to accurately model human-relevant disease progression and complications related to obesity and diabetes here!
BiochemAR: an augmented reality app for easy visualization of virtual 3D molecular models
BiochemAR: an augmented reality app for easy visualization of virtual 3D molecular models
Have you played Pokemon Go? Then you've used Augmented Reality (AR) technology! AR technology holds substantial promise and potential for providing a low-cost, easy to use digital platform for the manipulation of virtual 3D objects, including 3D models of biological macromolecules.