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 How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>