Featured Research

from universities, journals, and other organizations

Stop and go – How the cell deals with transcriptional roadblocks

Date:
February 23, 2011
Source:
Ludwig-Maximilians-Universitaet Muenchen (LMU)
Summary:
Gene transcription, the readout of genetic information, is a fundamental biological process. Researchers have now captured the blockade and reactivation of transcription on film. The findings have implications for understanding gene activation in stem cells and tumor cells.

Gene transcription, the readout of genetic information, is a fundamental biological process. Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have now captured the blockade and reactivation of transcription on film. The findings have implications for understanding gene activation in stem cells and tumor cells.

Gene transcription is central to cell function, as it converts the information stored in the DNA into RNA molecules of defined sequence, which then program protein synthesis. The enzyme RNA polymerase II (Pol II) is responsible for this genetic readout, but is prone to transcriptional arrest. The biochemist Professor Patrick Cramer, Director of LMU's Genzentrum, and his research associate Dr. Alan Cheung have now shown for the first time -- and captured on film -- what happens when Pol II arrests at a "roadblock." They were even able to observe how transcript is reactivated. Reactivation of arrested transcriptional complexes is a normal part of the readout process, and is therefore of fundamental significance in all cells. Indeed, as Patrick Cramer points out, "It is also utilized to regulate gene activity in stem and tumor cells."

According to Patrick Cramer, "DNA itself is a silent molecule." It takes the enzyme RNA polymerase II to bring it to life. Pol II is the molecular machine that transcribes the genetic information encoded in the DNA into molecules of messenger RNA (mRNA).

These in turn act as blueprints for the synthesis of proteins, whose structures are specified by the nucleotide sequences of the mRNAs. Since proteins, which include enzymes like Pol II, carry out most functions in cells, the process of transcription is essential for life. Transcription is highly complex and easily perturbed. Misincorporated nucleotides and other errors are quite frequent and can cause the enzyme to arrest. In such a case, Pol II often moves in retrograde, sliding a short distance in the opposite direction along the DNA, so that the defect can be repaired.

As soon as such proofreading takes place, the enzyme restarts. Sometimes, however, the enzyme moves too far backwards, and the RNA it has just synthesized gets jammed in a binding pocket. This brings the transcription process to a complete halt, and Pol II then requires the transcription factor TFIIS to get it moving again. TFIIS alters the shape of the active center of the enzyme, so that the tangled stretch of RNA can be excised, and transcription then resumes, with Pol II synthesizing that segment again. Cramer and Cheung have dissected the mechanism of blockade and reactivation in molecular detail -- and recorded it on film. Among other insights, it emerged that TFIIS not only displaces the trapped segment of mRNA, it also facilitates its excision.

"This process occurs in all cells all the time, and is essential for their survival," says Cramer. "In addition, in higher organisms, it is utilized to regulate gene activity, particularly in stem cells and tumor cells. Pol II performs a central function in cells, and is therefore the focus of my research. My approach is increasingly influenced by systems biology, and aims to elucidate the transcriptional network of the cell and describe it in molecular and mechanistic terms." (göd/suwe) The project was carried out under the auspices of the Center for Integrated Proein Science Munich (CiPSM) and the Nanosystems Initiative Munich (NIM).


Story Source:

The above story is based on materials provided by Ludwig-Maximilians-Universitaet Muenchen (LMU). Note: Materials may be edited for content and length.


Journal Reference:

  1. Alan C. M. Cheung, Patrick Cramer. Structural basis of RNA polymerase II backtracking, arrest and reactivation. Nature, 2011; DOI: 10.1038/nature09785

Cite This Page:

Ludwig-Maximilians-Universitaet Muenchen (LMU). "Stop and go – How the cell deals with transcriptional roadblocks." ScienceDaily. ScienceDaily, 23 February 2011. <www.sciencedaily.com/releases/2011/02/110223133442.htm>.
Ludwig-Maximilians-Universitaet Muenchen (LMU). (2011, February 23). Stop and go – How the cell deals with transcriptional roadblocks. ScienceDaily. Retrieved September 16, 2014 from www.sciencedaily.com/releases/2011/02/110223133442.htm
Ludwig-Maximilians-Universitaet Muenchen (LMU). "Stop and go – How the cell deals with transcriptional roadblocks." ScienceDaily. www.sciencedaily.com/releases/2011/02/110223133442.htm (accessed September 16, 2014).

Share This



More Plants & Animals News

Tuesday, September 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Some Tobacco Farmers Thrive Amid Challenges

Some Tobacco Farmers Thrive Amid Challenges

AP (Sep. 16, 2014) — The South's tobacco country is surviving, and even thriving in some cases, as demand overseas keeps growers in the fields of one of America's oldest cash crops. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

Scientists Given Rare Glimpse of 350-Kilo Colossal Squid

AFP (Sep. 16, 2014) — Scientists say a female colossal squid weighing an estimated 350 kilograms (770 lbs) and thought to be only the second intact specimen ever found was carrying eggs when discovered in the Antarctic. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com
Raw: Scientists Examine Colossal Squid

Raw: Scientists Examine Colossal Squid

AP (Sep. 16, 2014) — Squid experts in New Zealand thawed and examined an unusual catch on Tuesday: a colossal squid. It was captured in Antarctica's remote Ross Sea in December last year and has been frozen for eight months. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

AFP (Sep. 16, 2014) — Since the arrival of Ebola in Ivory Coast, Ivorians have been abandoning their pets, particularly monkeys, in the fear that they may transmit the virus. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins