Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Non-specific and Specific RNA Binding Proteins Found to be Fundamentally Similar

09.10.2013
Nature Study Shows Distinct Behavior of Proteins Reflects Common Biochemical Principles

Researchers from Case Western Reserve University School of Medicine have found unexpected similarities between proteins that were thought to be fundamentally different.

The team studied how proteins bind to RNA, a process required for gene expression. It is known that some proteins only bind RNAs with certain sequences. Other proteins have been deemed “non-specific” because they interact with RNAs at seemingly random places. But the Case Western Reserve team has published a new study in Nature showing that non-specific proteins actually do have the ability to be specific about where they bind to RNA – seeking out and binding with particular sequences of nucleotides.

“There seems to be no such thing as specific or non-specific proteins; in essence, they are all specific. But they use their specificity differently,” said Eckhard Jankowsky, PhD, co-senior author and professor in the Center for RNA Molecular Biology at the School of Medicine. “Our findings advance understanding of how proteins and nucleic acids control gene expression, which leads to insights into how this control is lost or altered in cancer, viral infections and other diseases.”

The Case Western Reserve research team developed a new method for measuring proteins binding to thousands of different RNA molecules, called High Throughput Sequencing Kinetics (HTS-KIN). Applicable to many biologic fields, the approach allows researchers to analyze large numbers of mutations at protein binding sites in DNA or RNA quickly. HTS-KIN allows scientists to complete experiments in days that previously would have taken years to finish.

“By combining traditional biochemical methods with next-generation sequencing technology, we can now do one experiment with thousands of different RNAs, while before we were limited to analyzing only one RNA molecule at a time,” said Michael E. Harris, PhD, co-senior author and associate professor of biochemistry at the School of Medicine.

Defects in the interactions between RNA and binding proteins underlie numerous human diseases including cancer and neurodegenerative diseases. This insight into how molecules interact is a critical step toward the development of novel strategies for treating human disease.

“The Case Western Reserve researchers’ new findings may suggest ways to design drugs targeting a whole class of proteins that bind to DNA and RNA at sites lacking specific recognition sequences, which would guide them into place. Previously, we didn't understand how these proteins recognized where to bind to DNA or RNA, which hampered the design of drugs targeting that activity," said Oleg Barski, PhD, of the National Institutes of Health's National Institute of General Medical Sciences, which partially funded the research. "The research also shows that next-generation sequencing technology can deepen our understanding of these proteins and how they control the inner workings of cells."

Jankowsky and Harris utilized HTS-KIN to analyze how weakly or tightly large numbers of different RNAs bind to a particular protein. Although non-specific proteins were predicted to bind to all RNA sequences with similar affinity, the researchers found the same broad range of binding affinities for the non-specific protein that typically appear for a specific protein.

The authors theorize that the two types of proteins may not differ fundamentally, but rather use different parts of their affinity spectrum in order to express genes correctly. While specific proteins can connect with their preferred sequences among a cell’s many RNA molecules, the preferred RNA sequences of non-specific proteins are not created by the cell. As a result, non-specific proteins are left to bind to the available RNAs with similar affinity for many different RNAs.

“Essentially, each protein has binding preferences. However, the non-specific proteins can bind only to those sequences that are made available to them, whereas the specific proteins are able to bind to their ‘first choice’ sequences,” added Jankowsky.

This study was supported by grants from National Institutes of Health: GM067700, GM099720, GM056740, GM096000, T32GM008056 and UL1RR024989.

View the Nature paper at link: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12543.html.

About Case Western Reserve University School of Medicine

Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and is among the nation's top medical schools for research funding from the National Institutes of Health. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century. Eleven Nobel Laureates have been affiliated with the school.

Annually, the School of Medicine trains more than 800 M.D. and M.D./Ph.D. students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News & World Report's "Guide to Graduate Education."

The School of Medicine's primary affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002.

Jessica Studeny | EurekAlert!
Further information:
http://www.case.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

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

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>