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 Insights into the origin of life: how the first protocells divided
19.02.2020 | Universität Augsburg

nachricht Superresolution live-cell imaging provides unexpected insights into the dynamic structure of mitochondria
18.02.2020 | Heinrich-Heine-Universität Düsseldorf

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

Im Focus: Skyrmions like it hot: Spin structures are controllable even at high temperatures

Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices

The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...

Im Focus: Making the internet more energy efficient through systemic optimization

Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.

Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.

Im Focus: New synthesis methods enhance 3D chemical space for drug discovery

After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.

"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.

Im Focus: Quantum fluctuations sustain the record superconductor

Superconductivity approaching room temperature may be possible in hydrogen-rich compounds at much lower pressures than previously expected

Reaching room-temperature superconductivity is one of the biggest dreams in physics. Its discovery would bring a technological revolution by providing...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

Time-resolved measurement in a memory device

19.02.2020 | Physics and Astronomy

Mixed-signal hardware security thwarts powerful electromagnetic attacks

19.02.2020 | Information Technology

Could water solve the renewable energy storage challenge?

19.02.2020 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>