Stop and go: How the cell deals with transcriptional roadblocks

Feb 23, 2011

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." (Nature online, 23 February 2011)

According to Patrick Cramer, "DNA itself is a silent molecule". It takes the enzyme 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 , 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 , 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 , 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".

Explore further: Scientists throw light on the mechanism of plants' ticking clock

More information: Structural basis of RNA polymerase II backtracking, arrest, and reactivation; Alan C.M. Cheung and Patrick Cramer, Nature online, February 23, 2011.

Provided by Ludwig-Maximilians-Universitat Munchen

not rated yet

Related Stories

Lab identifies new role for factor critical to transcription

Jun 17, 2008

The Stowers Institute's Shilatifard Lab has identified a new role for the elongation factor ELL in gene transcription by RNA polymerase II (Pol II) — the enzyme that synthesizes messenger RNA to carry genetic information ...

How RNA polymerase II gets the go-ahead for gene transcription

Oct 09, 2009

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 ...

Recommended for you

Fighting bacteria—with viruses

Jul 24, 2014

Research published today in PLOS Pathogens reveals how viruses called bacteriophages destroy the bacterium Clostridium difficile (C. diff), which is becoming a serious problem in hospitals and healthcare institutes, due to its re ...

Atomic structure of key muscle component revealed

Jul 24, 2014

Actin is the most abundant protein in the body, and when you look more closely at its fundamental role in life, it's easy to see why. It is the basis of most movement in the body, and all cells and components ...

Brand new technology detects probiotic organisms in food

Jul 23, 2014

In the food industr, ity is very important to ensure the quality and safety of products consumed by the population to improve their properties and reduce foodborne illness. Therefore, a team of Mexican researchers ...

Protein evolution follows a modular principle

Jul 23, 2014

Proteins impart shape and stability to cells, drive metabolic processes and transmit signals. To perform these manifold tasks, they fold into complex three-dimensional shapes. Scientists at the Max Planck ...

User comments : 0