PRESS-NEWS.org - Press Release Distribution
FREE PRESS RELEASES DISTRIBUTION

'Activating' RNA takes DNA on a loop through time and space

Links for disease and role in embryonic development

2013-02-18
(Press-News.org) Long segments of RNA— encoded in our DNA but not translated into protein—are key to physically manipulating DNA in order to activate certain genes, say researchers at The Wistar Institute. These non-coding RNA-activators (ncRNA-a) have a crucial role in turning genes on and off during early embryonic development, researchers say, and have also been connected with diseases, including some cancers, in adults.

In an online article of the journal Nature, a team of scientists led by Wistar's Ramin Shiekhattar, Ph.D., detail the mechanism by which long non-coding RNA-activators promote gene expression. They show how these RNA molecules help proteins in the cell to create a loop of DNA in order to open up genes for transcription. Their experiments have also described how particular ncRNA-a molecules are related to FG syndrome, a genetic disease linked to severe neurological and physical deficits. "These ncRNA-activators can activate specific genes by working with large protein complexes, filling in a big piece of the puzzle," said Shiekhattar, Herbert Kean, M.D., Family Professor and senior author of the study. "Our DNA encodes thousands of these ncRNA-activators, each with a role in timing the expression of a specific gene. As we learn more about non-coding RNA, I believe we will have a profoundly better understanding of how our genes function."

Their findings also provide a plausible mechanism of how locations along chromosomes, classically known as "enhancer" elements, can influence the expression ("reading") of genes located 5,000 to 100,000 base pairs ("letters") of DNA away. According to their findings, ncRNA-a molecules bind to large protein complexes to form a loop of DNA, which then opens up the gene to the molecular machinery that transcribes DNA. "There is an abundance of evidence to indicate that enhancers are critical components of transcription during embryonic development and disease process," Shiekhattar said.

"Non-coding RNAs are probably one of the earliest molecules that determine spatial and temporal gene expression in a developing embryo," Shiekhattar said. "These enhancers can help turn genes on and off as a growing embryo would need, but as we have seen in other genetic mechanisms of embryonic development, they can lead to cancer if they are switched on inappropriately in adult cells." In the classic "central dogma" of biology, chromosomal DNA is transcribed into RNA, which is then translated by the cell into proteins. In recent years, however, scientists have found that not all transcribed RNA molecules become translated into proteins. In fact, studies have shown that large portions of the genome are transcribed into RNA that serve tasks other than functioning as blueprints for proteins. In 2010, the Shiekhattar lab first published the discovery of these ncRNA enhancer molecules in the journal Cell (2010 Oct 1;143(1):46-58), and theorized on their role as "enhancers" of gene expression. Since then, laboratories around the world have published and linked ncRNAs not only to transcriptional enhancers but also to certain diseases, including some cancers. To discover how such enhancer-like RNAs function, the Shiekhatter laboratory deleted candidate molecules with known roles in activating gene expression, and assessed if they were related to RNA-dependent activation. They found that depleting components of the protein complex known as Mediator specifically and potently diminished the ability of ncRNA-a to start the process of transcribing a gene into RNA. Further, they found that these activating ncRNAs can attach to Mediator at multiple locations within the Mediator protein complex, and Mediator itself can interact with the enhancer element site on DNA that encodes these activating ncRNAs. Their results also determined how mutations in a protein that makes up the Mediator complex, called MED12, drastically diminishes Mediator's ability to associate with activating ncRNAs.

Mutations in the MED12 protein are a marker for FG syndrome (also know as Opitz–Kaveggia syndrome), a rare genetic disorder that leads to abnormalities throughout the body and varying degrees of physical and neurological problems. "This clearly shows how activating ncRNAs can influence disease development, an idea that has been gaining evidence in the scientific literature," Shiekhattar said. To confirm that ncRNA-a works with Mediator to form a loop in DNA, the researchers used a technique called chromosome conformation capture (3C) to gain a better understanding of the three-dimensional structure of chromosomes. Their results show how Mediator gets a foothold of sorts on the portion of DNA that encodes the ncRNA-a, and twists the DNA to form a loop.

"The looping mechanism serves to physically bring together a distant enhancer element with the start site of the targeted gene, allowing Mediator to recruit the proteins responsible for reading the gene to the location," Shiekhattar said. "It is at least one answer to how these classical enhancer elements function while being physically distant from their target genes."

### The Shiekhattar laboratory is supported by grants from the National Institutes of Health (P30 CA 010815). Wistar co-authors include Fan Lai, Ph.D., lead author, and Matteo Cesaroni, Ph.D., postdoctoral fellows in the Shiekhattar laboratory. Co-authors include Ulf Andersson Ørom, Ph.D., Max Planck Institute for Molecular Genetics; Malte Beringer, Ph.D., Center de Regulacio Genomica, Barcelona; Dylan J. Taatjes, Ph.D., University of Colorado; and Gerd A. Blobel, M.D., Ph.D., The Children's Hospital of Philadelphia. END


ELSE PRESS RELEASES FROM THIS DATE:

Dopants dramatically alter electronic structure of superconductor

2013-02-18
UPTON, NY - Over the last quarter century, scientists have discovered a handful of materials that can be converted from magnetic insulators or metals into "superconductors" able to carry electrical current with no energy loss-an enormously promising idea for new types of zero-resistance electronics and energy-storage and transmission systems. At present, a key step to achieving superconductivity (in addition to keeping the materials very cold) is to substitute a different kind of atom into some positions of the "parent" material's crystal framework. Until now, scientists ...

'Snooze button' on biological clocks improves cell adaptability

2013-02-18
The circadian clocks that control and influence dozens of basic biological processes have an unexpected "snooze button" that helps cells adapt to changes in their environment. A study by Vanderbilt University researchers published online Feb. 17 by the journal Nature provides compelling new evidence that at least some species can alter the way that their biological clocks function by using different "synonyms" that exist in the genetic code. "This provides organisms with a novel and previously unappreciated mechanism for responding to changes in their environment," said ...

Microbes team up to boost plants' stress tolerance

2013-02-18
UNIVERSITY PARK, PA. -- While most farmers consider viruses and fungi potential threats to their crops, these microbes can help wild plants adapt to extreme conditions, according to a Penn State virologist. Discovering how microbes collaborate to improve the hardiness of plants is a key to sustainable agriculture that can help meet increasing food demands, in addition to avoiding possible conflicts over scare resources, said Marilyn Roossinck, professor of plant pathology and environmental microbiology, and biology. "It's a security issue," Roossinck said. "The amount ...

Ancient teeth bacteria record disease evolution

2013-02-18
DNA preserved in calcified bacteria on the teeth of ancient human skeletons has shed light on the health consequences of the evolving diet and behaviour from the Stone Age to the modern day. The ancient genetic record reveals the negative changes in oral bacteria brought about by the dietary shifts as humans became farmers, and later with the introduction of food manufacturing in the Industrial Revolution. An international team, led by the University of Adelaide's Centre for Ancient DNA (ACAD) where the research was performed, has published the results in Nature Genetics ...

Wiring the ocean

2013-02-18
For most people, the sea is a deep, dark mystery. That is changing, though, as scientists find innovative ways to track the movements of ocean-going creatures. Stanford marine sciences professor and Stanford Woods Institute Senior Fellow Barbara Block is using technology to enable live feeds of animal movements relayed by a series of "ocean WiFi hotspots." This could help protect marine ecosystems by revolutionizing how we understand their function, population structure, fisheries management and species' physiological and evolutionary constraints. Block will explain ...

Excessive TV in childhood linked to long-term antisocial behaviour

2013-02-18
Children and adolescents who watch a lot of television are more likely to manifest antisocial and criminal behaviour when they become adults, according to a new University of Otago, New Zealand, study published online in the US journal Pediatrics. The study followed a group of around 1000 children born in the New Zealand city of Dunedin in 1972-73. Every two years between the ages of 5 and 15, they were asked how much television they watched. Those who watched more television were more likely to have a criminal conviction and were also more likely to have antisocial ...

Pathway controlling cell growth revealed

Pathway controlling cell growth revealed
2013-02-18
A Melbourne-based research team has discovered a genetic defect that can halt cell growth and force cells into a death-evading survival state. The finding has revealed an important mechanism controlling the growth of rapidly-dividing cells that may ultimately lead to the development of new treatments for diseases including cancer. The discovery was made by Associate Professor Joan Heath, Dr Yeliz Boglev and colleagues at the Melbourne-Parkville Branch of the Ludwig Institute for Cancer Research. Dr Kate Hannan, Associate Professor Rick Pearson and Associate Professor ...

Douglas A. Melton to Keynote present at Stem Cell Summit - Apr 2013 in Boston MA

2013-02-18
Douglas A. Melton will give a keynote presentation on "How To Make Pancreatic Beta Cells" at the Stem Cell Summit 2013 (Apr 29-30, 2013 in Boston MA). Dr. Melton's presentation will focus on the research of making human pancreatic beta cells to study and treat diabetes. This goal is pursued with two main approaches: directing the differentiation of stem cells into beta cells and studying the signals that replicate pre-existing beta cells. The signals that direct stem and progenitor cells toward a mature beta cell phenotype will be described as well as work ...

Abbey Design Center Wins Talk of the Town Award for Customer Satisfaction

2013-02-18
Achieving the highest customer satisfaction rating of 5 stars, Abbey Design Center has won the prestigious CMUS Talk of the Town Customer Satisfaction Award in the Home Improvement & Remodeling category. The Talk of the Town Awards, presented by Talk of the Town News, Customer Care News magazine and Celebration Media U.S. (CMUS), honor companies and professionals that provide excellent customer service as reported by their customers through no-cost, user-review websites, blogs, social networks, business rating services, and other honors and accolades. This data ...

Tennessee Roofer Creates New Nashville Focused Consumer Website

2013-02-18
Nashville Roofing Master, a Tennessee based roofing contractor, has announced the creation of a new website. The new site, Roofing-Nashville.net, is designed to provide consumer advice for homeowners and residents of the Nashville metro area and the surrounding region. The site features articles on various topics which will be of interest to people who need a new roof or repairs to their current roof. Prior to launching the new site, Roofing Master had a site which was more focused on marketing the strengths of the company, but which didn't have any content featuring ...

LAST 30 PRESS RELEASES:

Scientists model 'true prevalence' of COVID-19 throughout pandemic

New breakthrough to help immune systems in the fight against cancer

Through the thin-film glass, researchers spot a new liquid phase

Administering opioids to pregnant mice alters behavior and gene expression in offspring

Brain's 'memory center' needed to recognize image sequences but not single sights

Safety of second dose of mRNA COVID-19 vaccines after first-dose allergic reactions

Changes in disparities in access to care, health after Medicare eligibility

Use of high-risk medications among lonely older adults

65+ and lonely? Don't talk to your doctor about another prescription

Exosome formulation developed to deliver antibodies for choroidal neovascularization therapy

Second COVID-19 mRNA vaccine dose found safe following allergic reactions to first dose

Plant root-associated bacteria preferentially colonize their native host-plant roots

Rare inherited variants in previously unsuspected genes may confer significant risk for autism

International experts call for a unified public health response to NAFLD and NASH epidemic

International collaboration of scientists rewrite the rulebook of flowering plant genetics

Improving air quality reduces dementia risk, multiple studies suggest

Misplaced trust: When trust in science fosters pseudoscience

Two types of blood pressure meds prevent heart events equally, but side effects differ

New statement provides path to include ethnicity, ancestry, race in genomic research

Among effective antihypertensive drugs, less popular choice is slightly safer

Juicy past of favorite Okinawan fruit revealed

Anticipate a resurgence of respiratory viruses in young children

Anxiety, depression, burnout rising as college students prepare to return to campus

Goal-setting and positive parent-child relationships reduce risk of youth vaping

New research identifies cancer types with little survival improvements in adolescents and young adul

Oncotarget: Replication-stress sensitivity in breast cancer cells

Oncotarget: TERT and its binding protein: overexpression of GABPA/B in gliomas

Development of a novel technology to check body temperature with smartphone camera

The mechanics of puncture finally explained

Extreme heat, dry summers main cause of tree death in Colorado's subalpine forests

[Press-News.org] 'Activating' RNA takes DNA on a loop through time and space
Links for disease and role in embryonic development