Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Oregon team zeroes in on RNA-binding in myotonic dystrophy

09.11.2007
Study helps to determine normal functioning, giving clues to how disease state happens

University of Oregon researchers have shed new light on the function of an RNA-regulating protein known as muscleblind, which when it misbehaves and binds to rogue RNA can lead to disease affecting roughly one in 8,000 people.

The study, which used a combination of biochemical, biophysical and cell culture studies, was placed online ahead of regular publication in the December issue of the journal RNA. When the findings were initially presented in September at the annual meeting of the Myotonic Dystrophy Foundation in Italy, the work garnered a $1,000 cash prize for outstanding research for lead author Bryan Warf, a UO doctoral student.

Misbehaving RNA can lead to myotonic dystrophy, an inherited condition that affects muscles and other body systems. It is the most commonly occurring form of adult onset muscular dystrophy with progressive muscle wasting as well as a variety of symptoms. An early symptom is the inability of muscles to relax after a simple handshake or gripping of a doorknob. It also can lead to cataracts, cardiac arrhythmia, insulin resistance and male infertility. It can be life-threatening in cases of early onset, particularly in children. Researchers believe that the numbers of a specific type of nucleotide expansions in a person's DNA gives rise to myotonic dystrophy.

... more about:
»MBNL »RNA »dystrophy »myotonic »structure »toxic

The UO findings apply to both known forms: DM1, which can manifest at any point in life, from birth to late 60s; and DM2, which more commonly surfaces in adulthood. While independent genes are responsible in each form, the same protein's interaction with RNA in the genes is implicated in both diseases.

"In a simplistic view, this disease is about this protein not functioning properly," Warf said. "So we've been trying to see what this protein does normally to keep us healthy and promote healthy development."

In their study, Warf and Andy Berglund, professor of chemistry and member of the Institute of Molecular Biology, focused on the RNA-splicing protein muscleblind-like (MBNL) and its interactions with both normal strands of RNA and disease-causing RNA that contains mismatched pairs of repeat nucleotides. RNA (ribonucleic acid) is much like translation software, a driver that serves as a messenger between DNA and proteins.

"Toxic RNA," as Berglund describes the mutated strands in the genome, is like a sentence that contains many extra misplaced copies of the word "the" within it. In their paper, Warf and Berglund found that MBNL binds to both normal and toxic forms of RNA. When bound to the toxic versions, MBNL ignores its other RNA targets and does not help process them normally, leading to disease. In earlier work, Berglund's lab solved the crystal structure of the toxic RNA.

In this new study, Warf and Berglund tested MBNL's interactions with both normal RNA and toxic RNA. They found that muscleblind has no preference for a toxic RNA that contains any type of pyrimidine-pyrimidine mismatch. Warf and Berglund were the first to articulate the structure of one of MBNL’s normal RNA targets. It had been thought that the structure of the toxic RNA was much different than the structure of a normal RNA target for MBNL, but Warf and Berglund showed that the two structures are actually quite similar.

"Through his studies," Berglund said, "Bryan has provided insight into how muscleblind may normally function. The dogma was that this protein was recognizing a complex structure in the toxic RNA, and normally it was recognizing a more simple RNA structure in regulating splicing. Bryan found the RNA that is normally recognized actually adopts a structure that looks a lot like the toxic RNA. Muscleblind recognizes both. The diseased RNA is mimicking the natural RNA."

Jim Barlow | EurekAlert!
Further information:
http://www.uoregon.edu

Further reports about: MBNL RNA dystrophy myotonic structure toxic

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Shallow soils promote savannas in South America

20.10.2017 | Earth Sciences

How Obesity Promotes Breast Cancer

20.10.2017 | Life Sciences

How the smallest bacterial pathogens outwit host immune defences by stealth mechanisms

20.10.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>