Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Newly identified mechanism for silencing genes points to possible anti-cancer strategies

18.05.2007
Genes provide the instructions used by the individual cells to produce the many different proteins that make up the body. Scientists are only beginning to appreciate, however, the extraordinary degree of control exercised over every step of the production process.

Only about 10 percent of human genes, for example, are actively producing proteins in a given cell at a given time. The remaining 90 percent are silenced by a various mechanisms that act to interfere with gene transcription into messenger RNA or translation of messenger RNA into protein.

In a new study published online May 16 in the journal Nature, a team of scientists at The Wistar Institute, Philadelphia, and the University of California, San Diego, report identification of an important new gene-silencing mechanism, one that blocks the cellular machinery responsible for translating messenger RNA into proteins at specific genes.

The findings suggests that small bits of RNA known as microRNAs, known to help regulate genes but not used for protein production, may be operating in a completely novel way to prevent genes from producing proteins. MicroRNAs have been implicated in a number of cancers, and the newly outlined gene-silencing mechanism offers promising potential targets for anti-cancer interventions.

... more about:
»Foundation »MicroRNAs »RNA »Shiekhattar »ribosome

“Some microRNAs closely match their sequences against particular messenger RNA sequences to target them for destruction,” explains Ramin Shiekhattar, Ph.D., a professor?in the Gene Expression and Regulation Program and the Molecular and Cellular Oncogenesis Program at Wistar and senior author on the new study. Currently, Shiekhattar is also an ICREA professor at the Centre for Genomic Regulation in Barcelona, Spain. “That’s one way we know that microRNAs can silence genes. That mechanism requires extraordinary specificity, however, and we suspected that microRNAs were also acting in some other way to inhibit gene translation into protein. By tracking the associations between molecules involved in generating microRNAs and other molecules in the cell, we uncovered an entirely new pathway, one that led us to a mechanism that blocks the cellular machinery that produces protein from messenger RNA.”

In earlier studies, Shiekhattar identified a three-molecule complex known as RISC and showed that it plays a vital role in generating microRNAs. In the current study, Shiekhattar and his colleagues extended those studies to find that RISC also interacts with another complex that includes molecules required to build functional ribosomes. Ribosomes are cellular organelles responsible for translating messenger RNA into protein. Closer investigation showed that the new complex also included a component called eIF6. This molecule is known to interfere with the proper assembly of ribosomes, which prevents them from doing the work of translating messenger RNA into protein.

“We wondered if certain microRNA-responsive genes might be attracting microRNAs that then recruited eIF6 to that location,” Shiekhattar says. “If so, the eIF6 would prevent the assembly of a competent ribosome, thus blocking messenger RNA translation at that gene. The result would be to silence that specific gene. We tested this idea in human cells and in worms and found it to be the case in both. Interestingly, this not only supported our hypothesis, but to see it in such different organisms also suggested that the mechanism involved has long been conserved in evolution.”

The lead author on the study is Thimmaiah P. Chendrimada at The Wistar Institute. The additional Wistar co-authors are David Baillat (also currently, at the Centre for Genomic Regulation in Barcelona, Spain) and Richard I. Gregory. Co-authors Xinjun Ji and Steve A. Liebhaber, who conducted the experiments involving human cells, are affiliated with the University of Pennsylvania. Kenneth J. Finn is with the University of California, San Diego, as is study collaborator Amy E. Pasquinelli, who performed the investigations involving the C. elegans worm.

The research was supported by the National Institutes of Health, the Searle Foundation, the V Foundation for Cancer Research, the Mathers Foundation, the Cooley’s Anemia Foundation, and the Commonwealth Universal Research Enhancement Program of the Pennsylvania Department of Health.

Gloria Lligadas | alfa
Further information:
http://www.crg.es

Further reports about: Foundation MicroRNAs RNA Shiekhattar ribosome

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton 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: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>