Nav: Home

Polymerases pause to help mediate the flow of genetic information

May 17, 2017

Kansas City, MO. -- Stop-and-go traffic is typically a source of frustration, an unneccesary hold-up on the path from point A to point B. But when it comes to the molecular machinery that copies our DNA into RNA, a stop right at the beginning of the path may actually be helpful. Recent research from the Stowers Institute for Medical Research shows that this stop prevents another machine from immediately following the first, presumably to better control the traffic and avoid later collisions.

Each time a gene is "turned on" or expressed, a molecule called RNA polymerase must position itself at a specific spot along the DNA and travel down its winding strands, transcribing the gene from start to finish. Scientists once thought that as soon as a polymerase got the signal to go, it would zoom to the finish line, like a car on a race track. But then they discovered that most polymerases pause shortly after they start, without a clear reason why.

In a study published online May 15, 2017, in Nature Genetics, Stowers researchers show that when one polymerase pauses on the track, it keeps other polymerases from entering the starting gate. Paradoxically, polymerases that pause for longer periods of time can mediate faster and more synchronized gene expression in response to the kinds of signals triggered by various stages of development or dysregulated in cancer.

"We discovered a traffic rule that appears to guide the process of transcription," says Stowers Associate Investigator Julia Zeitlinger, Ph.D., who led the study. "Genes are transcribed through bursts of activity, like rush hour. Traffic is pretty dangerous. It makes sense to tightly control the number of cars on the road and minimize the number of accidents."

Genetic information flows from DNA to RNA to protein. Because transcription is the first step "to making practically everything" in the cell, Zeitlinger says, it has been an intense area of study for decades. Thousands of studies have focused on the initiation of transcription, when the polymerase first assembles itself on the DNA. But over the last ten years, scientists have come to realize that polymerases spend much of their time a short distance down from the starting gate, as if delayed by a caution flag.

Zeitlinger wondered how this pausing related to initiation, and what kind of an effect it had on the overall transcription process. In this study, Predoctoral Researcher Wanqing Shao used a method called ChIP-nexus developed by the Zeitlinger Lab to map the position of polymerases on the DNA, both in the presence and absence of drugs that block transcription. She found that paused polymerases were far more stable than polymerases assembled at the initiation site. In addition, Shao showed that paused polymerases kept new polymerases from initiating transcription.

This finding could be particularly important in the context of transcription bursts, a rapid succession of numerous transcribing polymerases interspersed by periods of inactivity that can last minutes or even hours. Since paused polymerases were observed to be so stable, the researchers think that they not only block other polymerases from immediately following them during bursts of transcription, but that they also sit there in between bursts of transcription.

"They are preventing other polymerases from lining up when the traffic lights are red and traffic is idle. The busy traffic only resumes when the cell needs more of this gene and turns the traffic lights green again," said Zeitlinger. "Having traffic rules makes sense. Leaving traffic to randomness would be inefficient and dangerous."

For example, cancer can arise when gene expression is allowed to unfold unchecked. Therefore, by understanding the basic mechanisms that control gene expression, researchers can gain a greater appreciation of the underlying causes of cancer and related diseases.
The work was funded by the Stowers Institute for Medical Research.

Lay Summary of Findings

In transcription, the first step of gene expression, the information stored in DNA is copied into RNA by a molecular machine known as RNA polymerase. Rather than hurriedly transcribing a gene from start to finish, these polymerases often pause as they travel down the double helix, sometimes for as long as an hour at a time. In a study published online May 15, 2017, in Nature Genetics, researchers at the Stowers Institute for Medical Research studied the effect this pausing had on the overall process of transcription. Predoctoral Researcher Wanqing Shao and her research advisor Julia Zeitlinger, Ph.D., show that when one polymerase pauses, it keeps other polymerases from initiating transcription. They believe that these pauses could provide a much-needed respite in between bursts of transcription to make gene expression more controlled and deliberate.

About the Stowers Institute for Medical Research

The Stowers Institute for Medical Research is a non-profit, basic biomedical research organization dedicated to improving human health by studying the fundamental processes of life. Jim Stowers, founder of American Century Investments, and his wife, Virginia, opened the Institute in 2000. Currently, the Institute is home to about 500 researchers and support personnel, over 20 independent research programs, and more than a dozen technology development and core facilities. Learn more about the Institute at and about its graduate program at

Stowers Institute for Medical Research

Related Dna Articles:

A new spin on DNA
For decades, researchers have chased ways to study biological machines.
From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.
Self-healing DNA nanostructures
DNA assembled into nanostructures such as tubes and origami-inspired shapes could someday find applications ranging from DNA computers to nanomedicine.
DNA design that anyone can do
Researchers at MIT and Arizona State University have designed a computer program that allows users to translate any free-form drawing into a two-dimensional, nanoscale structure made of DNA.
DNA find
A Queensland University of Technology-led collaboration with University of Adelaide reveals that Australia's pint-sized banded hare-wallaby is the closest living relative of the giant short-faced kangaroos which roamed the continent for millions of years, but died out about 40,000 years ago.
DNA structure impacts rate and accuracy of DNA synthesis
DNA sequences with the potential to form unusual conformations, which are frequently associated with cancer and neurological diseases, can in fact slow down or speed up the DNA synthesis process and cause more or fewer sequencing errors.
Changes in mitochondrial DNA control how nuclear DNA mutations are expressed in cardiomyopathy
Differences in the DNA within the mitochondria, the energy-producing structures within cells, can determine the severity and progression of heart disease caused by a nuclear DNA mutation.
Switching DNA and RNA on and off
DNA and RNA are naturally polarised molecules. Scientists believe that these molecules have an in-built polarity that can be reoriented or reversed fully or in part under an electric field.
New DNA synthesis technique promises rapid, high-fidelity DNA printing
Today, DNA is synthesized as an organic chemist would, using toxic chemicals and error-prone steps that limit accuracy and thus length to about 200 base pairs.
The changing shape of DNA
The shape of DNA can be changed with a range of triggers including copper and oxygen - according to new research from the University of East Anglia.
More Dna News and Dna Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.