Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Living View in Animals Shows How Cells Decide To Make Proteins

04.12.2006
Scientists at Duke University Medical Center have visualized in a living animal how cells use a critical biological process to dice and splice genetic material to create unique and varied proteins.

The scientists say the findings, made in mice, help explain a key wonder of human biology: how the same genes found in every cell of an individual's body can produce different proteins in different tissues and organs. These varied proteins, in turn, dictate the function of each tissue or organ.

The findings also may offer insight into a number of diseases, including cancer, in which the genetic process -- called alternative splicing -- goes awry and produces the wrong proteins, the scientists said.

The scientists published the findings in the Dec. 1, 2006, issue of the journal RNA. The study was funded by the National Institutes of Health.

... more about:
»Garcia-Blanco »IIIb »RNA »silencer

Scientists previously have examined alternative splicing in cells and tissues in test tubes, but this study marks its first successful visualization in a living mammal, said senior investigator Mariano Garcia-Blanco, M.D., Ph.D., a professor of molecular genetics and microbiology.

"We were able to watch alternative splicing as it occurred in different tissues," he said. "It's an excellent example of how experiments in living organisms provide a much more complete picture of how genes and proteins behave than do experiments using cells in culture."

Until 20 years ago, scientists believed that a single gene made a single protein. With the discovery of alternative splicing, it became clear that one gene can produce multiple proteins.

In alternative splicing, microscopic "scissors" in a gene chop the genetic material RNA into bits called "exons" and then reassemble the bits in a different order to form a new RNA molecule. In the process, some of the exons are retained while others are excluded. The exons that are retained in the final RNA determine which proteins the RNA produces within the cell.

The scissors that do the genetic chopping are, in most cells, proteins called splicing silencers and splicing enhancers.

In the current study, Garcia-Blanco's team sought to identify which silencers chop out an important segment of RNA in a gene called fibroblast growth receptor 2 (FGFR2). This gene plays a critical role in normal mouse and human development, and the order in which its RNA is assembled can alter an animal's development.

As a model system to study, the scientists genetically created a "glowing" mouse. The mouse carried in its FGFR2 gene a green fluorescent tag that would glow when a common type of silencer, called an "intronic silencer," chopped out a specific exon, called IIIb.

In this way, the scientists could track whether intronic silencers were chopping out the IIIb exon -- and if so, in which tissues and organs -- or whether other types of silencers or helper proteins were involved.

By tracking the green glow, the team found that cells in most tissues made the same decision to silence exon IIIb, but the cells used a variety of silencers and helper proteins to accomplish this task, said Vivian I. Bonano, a graduate student in the University Program in Genetics and Genomics and lead author of the journal report.

"Identifying which silencers are active in a given tissue or organ will ultimately help scientists understand how exons are erroneously included or excluded in various disease processes," Bonano said.

For example, a cell's decision to include exon IIIb is critical because the exon's presence or absence determines which variant of the FGFR2 protein is produced, she said. Such subtle variations in proteins can alter the cell's behavior, just as switching ingredients in a favorite recipe can change the food's flavor, according to the scientists.

"Viewing these decisions is most relevant in a living animal, because cells behave differently in their natural environment versus an artificially created environment such as a laboratory tissue culture," Garcia-Blanco said. "The complexity of alternative splicing necessitates its visualization as the decisions are occurring, because taking a cell out of its context shows only its current status and not how it arrived at that place."

For instance, the splicing process can change even from day to day as an animal develops, he said, adding that extracting cells and watching them in a culture cannot convey all of these transient changes.

Moreover, different cell types within the brain or other organs can exhibit different splicing decisions, Garcia-Blanco said. For example, neurons reside next to glial cells in the brain, yet they express different proteins in different amounts, and detecting such differences in cell cultures can be exceedingly difficult, he said.

"This is a powerful tool to apply to mouse genetics to learn when and where in the animals' bodies alternative splicing decisions are made and, eventually, to learn what factors are critical in making these decisions," Garcia-Blanco said.

"Given the importance of alternative splicing in health and disease," he added, "this anatomic mapping of splicing decisions may give us considerable insight into the many human diseases associated with improper regulation of splicing."

Becky Levine | EurekAlert!
Further information:
http://www.mc.duke.edu

Further reports about: Garcia-Blanco IIIb RNA silencer

More articles from Life Sciences:

nachricht Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>