Featured Research

from universities, journals, and other organizations

How RNA Polymerase II Gets The Go-ahead For Gene Transcription

Date:
October 9, 2009
Source:
Ludwig-Maximilians-Universität München
Summary:
The central dogma of molecular biology states that genes make RNAs, which then make proteins. Researchers in Germany have now discovered how the crucial first steps in RNA synthesis are executed -- and gene transcription is initiated.

All cells perform certain basic functions. Each must selectively transcribe parts of the DNA that makes up its genome into RNAs that specify the structure of proteins. The set of proteins synthesized by a cell in turn determines its structure and behaviour, and enables it to survive and reproduce. So it is crucial that the appropriate stretches of DNA are transcribed in each cell type.

Related Articles


In the current issue of the journal Nature, a team of researchers at the Gene Center of Ludwig-Maximilians-Universität (LMU) in Munich, led by Professor Patrick Cramer, provides the first detailed description of how the RNA polymerase II initiates gene transcription. "The findings led us to propose a model of the whole complicated process of transcription initiation," says Cramer. "This operation is of crucial importance in all organisms, because it determines which genes are expressed, and when. Our work thus represents a milestone in the quest to understand gene regulation."

Cell types such as liver cells and nerve cells differ from one another because they make distinct sets of proteins. Therefore, gene transcription and protein synthesis must be carried out with great precision. This requires the use of complicated assemblies made up of many different proteins, often referred to as molecular machines. The basic structure of RNA polymerase II, the protein complex that transcribes genes encoding proteins in multicellular organisms, was worked out some years ago, but this structure could not explain how the initial steps in transcription take place.

Signals encoded in the DNA sequence tell RNA polymerase II where to start and stop transcription. The regions in which transcription begins are called promoters. In many genes, the promoter region is marked by a short DNA sequence called the TATA box. The actual transcription start site (TSS) is located 30-40 nucleotides downstream. It was already known that the protein TBP recognizes and binds to the TATA box, producing a sharp kink in the DNA. TBP in turn binds TFIIB, to which the polymerase enzyme (comprising 12 different proteins) then attaches. So it is TFIIB that actually gives the start signal for transcription initiation.

What the LMU researchers in Cramer's group have now done is to determine the three-dimensional structure of the complex formed between RNA polymerase II and TFIIB from brewer's yeast. Analysis of this complex using X-ray diffraction gave them a map that could be compared with one obtained for the polymerase alone. The differences between the two enabled the scientists to localize the TFIIB with respect to both the polymerase and the DNA. On the basis of this structure they were able to deduce how the initiation of transcription occurs, how the TSS is selected and the first segment of RNA is synthesized and, finally, how the polymerase "shifts gear" from the initiation to the elongation mode, as it leaves the region of the promoter and proceeds on through the gene. In a fruitful collaboration with Professor Michael Thomm's lab at the University of Regensburg the researchers also confirmed important aspects of their model experimentally.

It turns out that TFIIB acts as a bridge between TBP and polymerase, so that the polymerase faces the DNA, in the so-called closed complex. This is converted into an open complex when part of the TFIIB (called the B-linker) inserts between the two DNA strands. One of the strands (the template strand) is displaced into a tunnel formed by TFIIB and the polymerase. The complex then searches the sequence in the tunnel for an initiator sequence that defines the TSS, "using a second element (the B-reader) in TFIIB, which functions rather like the reading head in a tape recorder", explains Cramer. When the TSS is located, the first two nucleotides of the new RNA transcript pair with their complementary partners on the DNA and are linked together by the polymerase. This marks the real initiation of transcription. After the addition of additional nucleotides, TFIIB is released from the complex.

The resulting elongation complex continues to synthesize an RNA sequence complementary to that of the template DNA strand, which later determines the structure of a specific protein. As Cramer points out, "The findings led us to propose a model of the whole complicated process of transcription initiation, an operation that is of crucial importance in all organisms, because it determines which genes are expressed, and when." The work of the LMU group thus represents a milestone in the quest to understand how genes are regulated. The results also provide the framework for investigating the mechanisms underlying the regulation of transcription initiation, which governs cellular gene expression. (PH)


Story Source:

The above story is based on materials provided by Ludwig-Maximilians-Universität München. Note: Materials may be edited for content and length.


Journal Reference:

  1. Dirk Kostrewa, Mirijam E. Zeller, Karim-Jean Armache, Martin Seizl, Kristin Leike, Michael Thomm and Patrick Cramer. RNA polymerase II-TFIIB structure and mechanism of transcription initiation. Nature, 2009; DOI: 10.1038/nature08548

Cite This Page:

Ludwig-Maximilians-Universität München. "How RNA Polymerase II Gets The Go-ahead For Gene Transcription." ScienceDaily. ScienceDaily, 9 October 2009. <www.sciencedaily.com/releases/2009/10/091009104646.htm>.
Ludwig-Maximilians-Universität München. (2009, October 9). How RNA Polymerase II Gets The Go-ahead For Gene Transcription. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2009/10/091009104646.htm
Ludwig-Maximilians-Universität München. "How RNA Polymerase II Gets The Go-ahead For Gene Transcription." ScienceDaily. www.sciencedaily.com/releases/2009/10/091009104646.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) — Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) — Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Why Your Boss Should Let You Sleep In

Why Your Boss Should Let You Sleep In

Newsy (Dec. 17, 2014) — According to research out of the University of Pennsylvania, waking up for work is the biggest factor that causes Americans to lose sleep. Video provided by Newsy
Powered by NewsLook.com
Flu Outbreak Closing Schools in Ohio

Flu Outbreak Closing Schools in Ohio

AP (Dec. 17, 2014) — A wave of flu illnesses has forced some Ohio schools to shut down over the past week. State officials confirmed one pediatric flu-related death, a 15-year-old girl in southern Ohio. (Dec. 17) Video provided by AP
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:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

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