Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Structure solved by Scripps scientists shows one way that body controls gene expression

16.02.2004


A group of scientists at The Scripps Research Institute has solved the structure of a protein that regulates the expression of genes by controlling the stability of mRNA -- an intermediate form of genetic information between DNA genes and proteins.

"Gene expression can be controlled at many levels, " says Scripps Research Professor Peter Wright, Ph.D., who is chairman of the Department of Molecular Biology and Cecil H. and Ida M. Green Investigator in Medical Research at Scripps Research. "One of them is at the level of the message."

The structure of the "tandem zinc finger" domain of the regulatory protein TIS11d in complex with a strand of mRNA was solved in the laboratory of Wright and H. Jane Dyson, Ph.D., by Maria A. Martinez-Yamout, Ph.D., of Scripps Research, and Brian P. Hudson, Ph.D., of Rutgers University. This is the first such structure to be solved, and it provides insights into the process of gene regulation at the atomic level.



In next month’s issue of Nature Structural & Molecular Biology, Wright and his colleagues describe the tandem zinc finger -- thus called because it contains two finger-like domains that must bind to zinc to fold into its active form. These tandem zinc fingers are a very common motif in mammalian genes, and hundreds of genes in the human genome contain some version of them. This diversity is perhaps indicative of the capability of TZF proteins to specifically recognize a large number of different RNA sequence motifs.

Insights into the workings of the regulatory protein TIS11d are particularly valuable because these proteins are involved in a number of fundamental biological processes, such as inflammation, and are potential targets for therapeutics in diseases where these processes go awry.

The Regulation of Genes at the mRNA Level

Regulation of gene expression in humans and other organisms is a crucial part of biology, and biology has a large repertoire of mechanisms for turning genes on and off. Many of the proteins encoded by genes in human and other genomes specialize in regulating other genes, often in complicated feedback mechanisms.

Shutting off the transcription of a gene -- the process whereby a single-stranded piece of messenger RNA (mRNA) is made from a double-stranded piece of DNA -- has for decades been recognized by molecular and cell biologists as a crucial way the cell regulates the expression of a gene.

In the last several years, many of these same scientists, including Wright and his colleagues, have been growing aware of the importance of post-transcriptional gene regulation, which occurs at the level of mRNA.

In mammals, once DNA genes are transcribed into mRNAs in the nucleus of a cell, they are usually transported outside the nucleus, where the mRNAs can be "translated" into proteins. At this point, certain regulatory proteins stabilize the mRNA, allowing it to be translated by the cell’s machinery into proteins. Other regulatory proteins destabilize the mRNAs, marking them for degradation by the cell’s machinery.

TIS11d belongs to a common family of regulatory proteins of this latter type. It regulates the levels of many important proteins involved in the body’s inflammatory response, such as tumor necrosis factor (TNF) and interferons, by marking the TNF and interferon mRNAs for destruction. With incredible specificity, this protein uses its tandem zinc finger domain to recognize particular sequences of TNF and interferon mRNA.

By solving the structure, Wright and his colleagues revealed for the first time in atomic detail exactly how this recognition occurs.

The TIS11d protein basically mimics the base-pairing that takes place in DNA by using its tandem zinc finger domains to bind to the mRNA. Following the same principle that two strands of DNA use to bind to each other, the TIS11d protein binds to the mRNA by forming hydrogen bonds with the Watson-Crick edges of the mRNA.

"It was remarkable to see how these tiny structures [work]," says Wright.

The research article "Recognition of the mRNA AU-rich element by the zinc finger domain of TIS11d" is authored by Brian P. Hudson, Maria A. Martinez-Yamout, H. Jane Dyson, and Peter E. Wright and appears in the March 2004 issue of Nature Structural & Molecular Biology.


The research was funded by the National Institutes of Health and The Skaggs Institute for Research.

About The Scripps Research Institute

The Scripps Research Institute in La Jolla, California, is one of the world’s largest, private, non-profit biomedical research organizations. It stands at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases and synthetic vaccine development.

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu/

More articles from Life Sciences:

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>