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!
Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care
Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses