Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists decode mystery sequences involved in gene regulation

11.07.2013
First-ever compendium of RNA sequences will be important guide to understanding the root of genetic diseases

Every cell in an organism's body has the same copy of DNA, yet different cells do different things; for example, some function as brain cells, while others form muscle tissue. How can the same DNA make different things happen? A major step forward is being announced today that has implications for our understanding of many genetically-linked diseases, such as autism.

Scientists know that much of what a gene does and produces is regulated after it is turned on. A gene first produces a molecule called RNA, to which tiny proteins called RNA binding proteins (RBPs) bind and control its fate. For instance, some of these proteins cut out parts of the RNA molecule so that it makes a particular protein, while other RBPs help destroy the RNA before it even produces a protein.

But these mechanisms are not well understood because the RNA sequences, which the RBPs bind to, have been so difficult to decipher. To fully understand gene regulation (and disregulation, as in the case of disease), scientists have needed to employ advanced lab techniques and data analysis to identify the patterns of the RNA sequences.

This gap in knowledge motivated a team of researchers co-led by Senior Fellow Tim Hughes (University of Toronto and the Canadian Institute for Advanced Research) to produce the first-ever compendium of RNA-binding sequences, which was published in Nature on July 11, 2013.

"It took us a long time to generate and analyze the data," explains Hughes. "After spending years developing and perfecting a method, we started looking at all the proteins in humans, fruit flies and other complex organisms that look like they may bind RNA and found which sequences they like to bind to. Our compendium of RNA-binding sequences will become a resource for researchers in this field, and will be especially useful in human genetic analysis."

The team found that humans and fruit flies have similar RBPs, since they derive from a common ancestor, and that in many cases they essentially bind the same sequences. The researchers anticipate that this is the case for proteins in other organisms.

"We looked at just over 200 proteins in total, but can probably infer the preference for tens of thousands of proteins in many other organisms," says Hughes.

In addition, many of the sequences similar across species were at the end of the RNA transcript, which is a region associated with regulation of RNA decay or movement of the RNA to another part of the cell. "This indicates that there is probably more regulation of gene expression itself at the level of stability or destruction of RNA," explains Hughes.

One of the major insights that came out of the team's analyses was about a well-studied protein called RBFOX1, which was already known to have a function in regulating RNA splicing and to be decreased in autism. The team's findings suggest that RBFOX1 has a role in regulating the expression level of nervous-system-related genes in brains with autism, and that it does so by making RNA more stable.

The underlying causes of disease are more complicated than a single gene not working right, says Hughes. He anticipates that the team's compendium will be useful in human genetic analysis.

"What often happens is that scientists identify a genetic variation associated with a disease, but then they don't understand why it leads to the disease. What exactly do these sequence changes cause? If the sequence is in a regulatory region of the RNA, then with our compendium, other scientists will be able to see what protein binds to it. This will give them a better idea of what is being disrupted."

The study was a large collaborative effort, supported in part by CIFAR, that involved Senior Fellows Brendan Frey (U of T) and Andrew Fraser (U of T) and Global Scholar Alumnus Matthew Weirauch (Cincinnati Children's Hospital Medical Center) in CIFAR's Genetic Networks program. Hamed Najafabadi (U of T), a postdoctoral fellow who performed much of the analysis in this study, was partially funded by CIFAR.

"Members of the Genetic Networks program have motivated us to look at roles for RNA-binding proteins causing disregulation of gene expression in disease," says Hughes. "We anticipate that this new knowledge will be valuable to other program members working on specific disorders."

The next steps for the team are to expand their compendium to encompass all complex organisms.

Frey also hopes to take these findings further to build models that will more accurately describe observed gene expression patterns.

"My research focuses on deciphering the regulatory sequences in DNA, which ultimately shape the fate of an RNA molecule," explains Frey. "I hope to take the RNA-binding sequences identified in this paper and use them as tokens to figure out how they act in a regulatory fashion. This will help us better understand human disease by providing insights into how a mutation in DNA affects regulation."

This work was supported by the U.S. National Institutes of Health, Canadian Institutes of Health Research, National Science and Engineering Research Council of Canada, CIFAR, and Human Frontier Science Program.

For more information, or to arrange an interview with Tim Hughes, please contact:

Margaret Mroziewicz at (416) 971-4876 or mmroziewicz@cifar.ca

About CIFAR

Established in 1982, CIFAR is an independent research institute comprising nearly 400 researchers from more than 100 academic institutions in 16 countries. The Genetic Networks program is one of CIFAR's multidisciplinary global research networks that is devoted to discovering how genes interact with one another, research that could identify the root causes of many complex genetic diseases, and lead to new treatments and preventive measures.

Margaret Mroziewicz | EurekAlert!
Further information:
http://www.cifar.ca

More articles from Life Sciences:

nachricht A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>