Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


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

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:

Further reports about: Foundation MicroRNAs RNA Shiekhattar ribosome

More articles from Life Sciences:

nachricht First time-lapse footage of cell activity during limb regeneration
25.10.2016 | eLife

nachricht Phenotype at the push of a button
25.10.2016 | Institut für Pflanzenbiochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

3-D-printed structures shrink when heated

26.10.2016 | Materials Sciences

Indian roadside refuse fires produce toxic rainbow

26.10.2016 | Health and Medicine

First results of NSTX-U research operations

26.10.2016 | Physics and Astronomy

More VideoLinks >>>