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 Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal
22.05.2018 | Friedrich-Alexander-Universität Erlangen-Nürnberg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Chemists at FAU successfully demonstrate imine hydrogenation with inexpensive main group metal

22.05.2018 | Life Sciences

Asian tiger mosquito on the move

22.05.2018 | Life Sciences

Self-illuminating pixels for a new display generation

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>