Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A new mechanism of regulating RNA degradation

28.01.2005


As any dedicated video game player knows, the first requirement for using a weapon or tool is finding it. And it is no different for cell biologists and clinicians who want to take control of gene expression in cells to create therapies to treat disease. While cells have a variety of ways to control gene expression, the trick for players in this game is to recognize them amidst the incredibly complex background of cellular machinery.



Now, in a paper in the January 28th issue of Cell, Lynne E. Maquat, Ph.D., professor of Biochemistry and Biophysics at the University of Rochester Medical Center, and her team have identified a novel pathway for RNA degradation, a form of regulation that has garnered significant attention in recent years, and one that has the potential to produce a new set of tools for physicians to use to fight disease.

Most of the gene-control tools researchers have collected thus far involve the first step in gene expression, in which DNA is copied into RNA transcripts. However, recent discoveries have shown that many of the tools cells use to regulate genes work after transcription, by moderating the activity and the life span of the RNA itself.


One major pathway for such post-transcriptional regulation is called nonsense-mediated decay (NMD). Originally NMD was thought to destroy incorrectly transcribed or otherwise problematic RNAs, but investigators now know that it plays a major role in regulating the life span of numerous RNAs, and thus controls gene activity.

To better understand what controls the NMD system, Maquat and her postdoctoral fellow, Yoon Ki Kim, Ph.D., used a critical component of the NMD complex, Upf1, as bait in a molecular fishing expedition. With this approach, proteins that naturally interact with the bait will be pulled out of the pool of cellular proteins.

They found that Upf1 grabbed onto Staufen1 (Stau1). Stau1 is a well-known RNA binding protein and some of its functions in the common fruit fly Drosophila are understood. "But no one knew what Staufen1 did in human cells," said Maquat, even though its presence in mammalian cells has been recognized for several years.

"We were surprised to find that Staufen1 interacts with Upf1," she added. "This is a whole new function for Staufen1 that couldn’t have been predicted from the studies in flies, even though a similar function may occur in flies."

The team discovered that Staufen1 doesn’t interact with other components of the NMD complex – and altering the amount of Staufen1 in the cell didn’t change NMD function. Those observations, said Maquat, sent Kim on a hunt for what Staufen1 and Upf1 were doing.

Looking at gene expression data available through the lab of Luc DesGroseillers, Ph.D. at the University of Montreal, they found that Staufen1 protein binds to numerous RNAs. Downregulating the amount of Staufen or Upf1 increased the half-life of these RNAs. Significantly, altering the amount of another NMD factor didn’t affect these RNAs.

Thus, Staufen1 and Upf1, together, degrade RNAs by a previously undescribed mechanism, which the team called Staufen1-mediated degradation (SMD). Preliminary results suggest that SMD activity affects numerous transcripts and, therefore, is a novel mechanism of gene regulation.

"We don’t yet understand how SMD is regulated but it must be," said Maquat. "Both Upf1 and Staufen1 can be phosphorylated, so their activities could be regulated by cell signaling pathways, such as those mediated by changes in growth conditions." That would allow the cell to differentially control the level of SMD-target RNAs, while leaving the NMD-regulated RNAs untouched.

This is likely to be the "tip of the iceberg" for Staufen1’s function in mammalian cells, said Maquat, and just the beginning of the SMD story as well.

Germaine Reinhardt | EurekAlert!
Further information:
http://www.urmc.rochester.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 >>>