(Press-News.org) PHILADELPHIA – Cells have their own version of the cut-and-paste editing function called splicing. Researchers at the University of Pennsylvania School of Medicine have documented a novel form of splicing in the cytoplasm of a nerve cell, which dictates a special form of a potassium channel protein in the outer membrane. The channel protein is found in the dendrites of hippocampus cells -- the seat of memory, learning, and spatial navigation -- and is involved in coordinating the electrical firing of nerve cells. Dendrites, which branch from the cell body of the neuron, play a key role in the communication between cells of the nervous system.
The diversity of proteins within the human body -- in this case neurons – arises from the many ways that messenger RNAs (mRNA) can be spliced and reconnected. To start, a gene is copied into mRNA, which contains both exons (protein-coding regions) and introns (non-coding regions). Special molecules cut out introns and merge together the remaining exon pieces, resulting in an mRNA capable of being translated into a specific protein.
The study, published this week online in the Proceedings of the National Academy of Sciences, is the first to show that introns that are retained in mRNA can direct the choice of protein sequences to be included in the final protein prior to translation into a full protein. Normally introns would be spliced out in the nucleus. Diseases such as epilepsy that are based on electrical misfiring in the brain could be targets of manipulation of such cytoplasmic splicing.
In a series of previously published research, the lab of senior author James Eberwine, PhD, established that splicing of RNA occurs outside of the nucleus in different parts of a nerve cell, specifically in the cytoplasm and dendrites. Eberwine is the Elmer Holmes Bobst professor of Pharmacology and co-director of the Penn Genome Frontiers Institute.
The group went on to discover that retained introns are necessary to produce a functional ion channel called BKCa in the dendrite. BKCa channels need to have these introns spliced out in the cytoplasm to work correctly. Introns were once thought of as junk DNA, but are now being shown to exert important regulatory control. Indeed, in some cases mutations in introns are responsible for causing disease, while in previous work Eberwine and colleagues were able to show that a retained intron is responsible for proper cellular localization of the final translated protein.
One particular intron, i17a, is found next to a portion of the BKCa protein, called the STREX domain. When STREX is in the channel protein BKCa, physiological properties such as burst firing and action potential change. These are important bio-electrical actions governing how nerve cells communicate with each other.
For the STREX domain to be part of the larger BKCa protein, i17a has to be removed in the cytoplasm. If i17a isn't spliced out in the cytoplasm very little STREX-containing BKCa protein is made. This leads to a poorly functioning neuron.
Diseases such as epilepsy that are based on electrical misfiring in the brain could be targets of manipulating cytoplasmic splicing to control how much STREX-containing BKCa protein is made and ultimately available in a neuron cell membrane. The diversity in splicing allows for different types of protein to be made, including the STREX-containing protein. In turn, other proteins are then able to bind to the channel, which in turn leads to other molecular events necessary for correct nerve firing.
The generality of this phenomena is being investigated with the goal being to understand this form of cellular regulation such that it can be experimentally manipulated in a directed and meaningful manner.
INFORMATION:
The first author is Thomas Bell, with other contributing authors including Kevin Miyashiro, Peter Buckley, Jeanine Jochems, Department of Pharmacology at Penn; Miler Lee and Junhyong Kim, Biology Department at Penn; Thomas Parsons, Penn School of Veterinary Medicine; and Ron McCullough and Charles Cantor, Sequenom, Inc.
This work was funded by an NIH Pioneer Award and grants from the NIH Director's fund and the National Institute on Aging.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $3.6 billion enterprise.
Penn's School of Medicine is currently ranked #2 in U.S. News & World Report's survey of research-oriented medical schools, and is consistently among the nation's top recipients of funding from the National Institutes of Health, with $367.2 million awarded in the 2008 fiscal year.
Penn Medicine's patient care facilities include:
The Hospital of the University of Pennsylvania – the nation's first teaching hospital, recognized as one of the nation's top 10 hospitals by U.S. News & World Report.
Penn Presbyterian Medical Center – named one of the top 100 hospitals for cardiovascular care by Thomson Reuters for six years.
Pennsylvania Hospital – the nation's first hospital, founded in 1751, nationally recognized for excellence in orthopaedics, obstetrics & gynecology, and psychiatry & behavioral health.
Additional patient care facilities and services include Penn Medicine at Rittenhouse, a Philadelphia campus offering inpatient rehabilitation and outpatient care in many specialties; as well as a primary care provider network; a faculty practice plan; home care and hospice services; and several multispecialty outpatient facilities across the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2009, Penn Medicine provided $733.5 million to benefit our community.
Process leading to protein diversity in cells important for proper neuron firing
Implications for brain diseases such as epilepsy, according to Penn study
2010-11-19
ELSE PRESS RELEASES FROM THIS DATE:
Does sex matter? It may when evaluating mental status
2010-11-19
Montreal, November 18, 2010 – Schizophrenia is a mental disorder that differs between the sexes in terms of age at onset, symptomatology, response to medication, and structural brain abnormalities. Now, a new study from the Université de Montréal shows that there is gender difference between men and women's mental ability – with women performing better than men. These findings, published recently in, Schizophrenia Research, have implications for the more than 300 000 affected Canadians.
"We are the first to report sex differences in brain function of schizophrenics," ...
10 years of Soufriere Hills Volcano research published
2010-11-19
The Soufriere Hills Volcano on Montserrat erupted in 1995, and an international team of researchers has studied this volcano from land and sea since then to understand the workings of andesite volcanos more completely.
"To the extent that the Soufriere Hills Volcano is typical of andesitic dome building volcanoes, results from this research can be expected to apply more generally," said Barry Voight, professor emeritus of geosciences, Penn State.
Voight and R. S. J. Sparks, the Channing Wills professor of geology, Bristol University, guest edited and introduced a special ...
E. coli infection linked to long-term health problems
2010-11-19
People who contract gastroenteritis from drinking water contaminated with E. coli are at an increased risk of developing high blood pressure, kidney problems and heart disease in later life, finds a study published on bmj.com today.
The findings underline the importance of ensuring a safe food and water supply and the need for regular monitoring for those affected.
It is estimated that E. coli O157:H7 infections cause up to 120,000 gastro-enteric illnesses annually in the US alone, resulting in over 2,000 hospitalisations and 60 deaths. However, the long term health ...
Researchers learn that genetics determine winter vitamin D status
2010-11-19
Vitamin D is somewhat of an unusual "vitamin," because it can be made in the body from sunlight and most foods do not contain vitamin D unless added by fortification. Synthesis of vitamin D in the body requires exposure to ultraviolet light and can be influenced by genetics, skin color, and sun exposure. Reports of greater than expected vitamin D insufficiency coupled with emerging evidence that higher circulating concentrations of this nutrient may protect against cardiovascular disease have prompted a renewed interest in teasing out how environment, genetics, and behavior ...
Why so many antibodies fail to protect against HIV infection
2010-11-19
DURHAM, NC – Researchers have been stymied for years over the fact that people infected with the AIDS virus do indeed produce antibodies in response to the pathogen – antibodies that turn out to be ineffective in blocking infection.
Now, scientists at Duke University Medical Center can explain why: Some of the earliest and most abundant antibodies available to fight HIV can't actually "see" the virus until after it's already invaded a healthy cell.
The scientists based their conclusion on the results of a series of crystallography and biochemical experiments that revealed ...
Economic downturn takes toll on health of Americans with heart disease, diabetes or cancer
2010-11-19
Boston, MA – A new poll from researchers at the Harvard School of Public Health (HSPH) and Knowledge Networks (KN) shows that many people with heart disease, diabetes or cancer believe the economic downturn is hurting their health and will have further negative impacts in the future. Many Americans with these illnesses face financial problems paying for medical bills in this economy. Most of these people do not believe the new national health care reform law (Patient Protection and Affordable Care Act 2010) will help them. This national poll is the first in a collaborative ...
Reduce the VAT on alcohol sold in pubs, says expert
2010-11-19
Alcoholic drinks served in pubs should be taxed at a lower level than drinks bought from shops, says an expert in this week's BMJ.
This action would deliver the health benefits associated with introducing a minimum price on alcohol, increase tax revenue for the Treasury and save pubs says Dr Nick Sheron.
The author is head of clinical hepatology at the University of Southampton, a member of the Alcohol Health Alliance and an advisor for the 2010 House of Commons Select Committee Report on Alcohol.
Sheron says lowering VAT for alcohol sold in pubs would solve the plight ...
LSUHSC reports first successful salivary stone removal with robotics
2010-11-19
New Orleans, LA – Dr. Rohan Walvekar, Assistant Professor of Otolaryngology Head and Neck Surgery, Director of Clinical Research and the Salivary Endoscopy Service at LSU Health Sciences Center New Orleans, has reported the first use of a surgical robot guided by a miniature salivary endoscope to remove a 20mm salivary stone and repair the salivary duct of a 31-year-old patient. Giant stones have traditionally required complete removal of the salivary gland. Building upon their success with the combination of salivary endoscopic guidance with surgery, Dr. Walvekar and his ...
Teenage girls face greater violence threat from poverty
2010-11-19
Living in a deprived area increases the risk of violence more sharply for girls than boys, according to a Cardiff University study of former industrial areas.
The new results suggest violence prevention strategies need to focus more on local inequalities, especially to protect vulnerable adolescent girls.
The survey was conducted by the Violence and Society Research Group at Cardiff University. The team studied nearly 700 young people, aged 11 to 17, who attended casualty departments in South Wales with injuries from violence. The researchers matched the patients against ...
Gene therapy for metastatic melanoma in mice produces complete remission
2010-11-19
INDIANAPOLIS – A potent anti-tumor gene introduced into mice with metastatic melanoma has resulted in permanent immune reconfiguration and produced a complete remission of their cancer, according to an article to be published in the December 2010 issue of the Journal of Clinical Investigation. The online version is now available.
Indiana University School of Medicine researchers used a modified lentivirus to introduce a potent anti-melanoma T cell receptor gene into the hematopoietic stem cells of mice. Hematopoietic stem cells are the bone marrow cells that produce all ...
LAST 30 PRESS RELEASES:
Insulin resistance is linked to over 30 diseases – and to early death in women, study of people in the UK finds
Innovative semaglutide hydrogel could reduce diabetes shots to once a month
Weight loss could reduce the risk of severe infections in people with diabetes, UK research suggests
Long-term exposure to air pollution and a lack of green space increases the risk of hospitalization for respiratory conditions
Better cardiovascular health in early pregnancy may offset high genetic risk
Artificial intelligence method transforms gene mutation prediction in lung cancer: DeepGEM data releases at IASLC 2024 World Conference on Lung Cancer
Antibody–drug conjugate I-DXd shows clinically meaningful response in patients with extensive-stage small cell lung cancer
IASLC Global Survey on biomarker testing reveals progress and persistent barriers in lung cancer biomarker testing
Research shows pathway to developing predictive biomarkers for immune checkpoint inhibitors
Just how dangerous is Great Salt Lake dust? New research looks for clues
Maroulas appointed Associate Vice Chancellor, Director of AI Tennessee
New chickadee research finds cognitive skills impact lifespan
Cognitive behavioral therapy enhances brain circuits to relieve depression
Terasaki Institute awarded $2.3 Million grant from NIH for organ transplantation research using organs-on-a-chip technology
Atoms on the edge
Postdoc takes multipronged approach to muon detection
Mathematical proof: Five satellites needed for precise navigation
Scalable, multi-functional device lays groundwork for advanced quantum applications
Falling for financial scams? It may signal early Alzheimer’s disease
Integrating MRI and OCT for new insights into brain microstructure
Designing a normative neuroimaging library to support diagnosis of traumatic brain injury
Department of Energy announces $68 million in funding for artificial intelligence for scientific research
DOE, ORNL announce opportunity to define future of high-performance computing
Molecular simulations, supercomputing lead to energy-saving biomaterials breakthrough
Low-impact yoga and exercise found to help older women manage urinary incontinence
Genetic studies reveal new insights into cognitive impairment in schizophrenia
Researcher develops technology to provide cleaner energy and cleaner water
Expect the unexpected: nanoscale silver unveils intrinsic self-healing abilities
nTIDE September 2024 Jobs Report: Gains in employment for people with disabilities appear to level off after reducing gaps with non-disabled workers
Wiley enhances NMR Spectral Library Collection with extensive new databases
[Press-News.org] Process leading to protein diversity in cells important for proper neuron firingImplications for brain diseases such as epilepsy, according to Penn study