Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Wistar researchers discover new class of objects encoded within the genome

07.10.2010
Despite progress in decoding the genome, scientists estimate that fully 95 percent of our DNA represents dark, unknown territory.

In the October 1 issue of the journal Cell researchers at The Wistar Institute shed new light on the genetic unknown with the discovery of the ability of long non-coding RNA (ncRNA) to promote gene expression.

The researchers believe these long ncRNA molecules may represent so-called gene enhancer elements—short regions of DNA that can increase gene transcription. While scientists have known about gene enhancers for decades, there has been no consensus about how these enhancers work.

These findings join a growing body of evidence that the classic “central dogma” of genetics is incomplete. In the central dogma, 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 whole swathes of the genome are transcribed for unknown reasons.

In the present study, the Wistar researchers pinpoint 3,000 long ncRNAs and estimate that there could be a total of between 10,000 to 12,000 long ncRNA sequences within our DNA. This number is comparable to the 20,000 genes that are known to encode proteins. Most long ncRNAs are encoded in DNA near genes known to be important to both stem cells and cancer. This observation also suggests that targeting ncRNAs may represent a new strategy in slowing cancer growth.

“We are excited, first of all, because this is a new discovery about the very nature of human DNA; a new class of genetic object and a new layer of genetic regulation,” said Ramin Shiekhattar, Ph.D., Wistar’s Herbert Kean, M.D., Family Professor and senior author of the study.

“Secondly, we may have solved, in part, a great mystery in modern genetics. These long non-coding RNA sequences may account for the activity of enhancer elements, which have been well-studied but never quite characterized,” Shiekhattar said.

Almost three years ago, while at the Centre for Genomic Regulation in Barcelona, Spain, Shiekhattar began a prospective hunt for non-coding RNA sequences using GENCODE, a database that annotates the human genome with currently available scientific evidence. After filtering out protein-coding transcripts and non-coding RNAs that might overlap known protein-coding genes, they found approximately 3,000 long ncRNA sequences. At the time, GENCODE only accounted for a third of the genome, so Shiekhattar estimates that there are likely more.

The researchers mapped the ncRNA sites within the genome, and found that ncRNAs tended to be located near genes that influence how stem cells change into other cell types. Shiekhattar and his colleagues then developed new assays to screen cell cultures for these ncRNA sequences, and discovered that ncRNAs were found extensively in a variety of cell types.

The idea that molecules of RNA can have a DNA-regulating effect is well established. More than 1,000 so-called microRNAs are known to science, for example, and their effect on silencing genes has been well described. According to Shiekhattar, he assumed that long ncRNAs would also silence genes, not promote their activation. To his surprise, the researchers found that depleting a cell of ncRNAs actually decreased the degree of overall gene expression of neighboring genes, revealing a role for ncRNAs in potentiating gene expression.

In fact, when Shiekhattar and his colleagues depleted adult stem cells of a specific long ncRNA, known as ncRNA-activating 7 (ncRNA-a7), it had the same effect as depleting the protein product of a nearby gene, Snai1, which regulates how the cells migrate. Their studies further showed that inserting an ncRNA next to a gene for luciferase—the enzyme responsible for a firefly’s glow—increased the amount of protein produced by that gene in cells grown in culture. While not all long ncRNAs may act like enhancers, the majority of the ones the team studied do, Shiekhattar says.

“We know long non-coding RNAs can promote gene expression, but what we need to know now is how they do it,” Shiekhattar said, “which is precisely the object of our ongoing research plan.”

Wistar co-authors include Ulf Andersson Ørom, Ph.D., first author and postdoctoral fellow in the Shiekhattar laboratory; Qihong Huang, M.D., Ph.D., a Wistar professor; Kiranmai Gumireddy, Ph.D., a senior staff scientist in the Huang laboratory; Malte Beringer, Ph.D., Alessandro Gardini, Ph.D., and Fan Lai, Ph.D., postdoctoral fellows in the Shiekhattar laboratory. Co-authors from the Centre for Genomic Regulation include Thomas Derrien, Ph.D., Giovanni Bussotti, Ph.D., Matthias Zytnicki, Ph.D., Cedric Notredame, Ph.D., and Roderic Guigo, Ph.D.

Funding for this study was provided by the National Institutes of Health, the American Italian Cancer Foundation, and the Danish Council for Independent Research.

The Wistar Institute is an international leader in biomedical research with special expertise in cancer research and vaccine development. Founded in 1892 as the first independent nonprofit biomedical research institute in the country, Wistar has long held the prestigious Cancer Center designation from the National Cancer Institute. The Institute works actively to ensure that research advances move from the laboratory to the clinic as quickly as possible. The Wistar Institute: Today’s Discoveries – Tomorrow’s Cures.

Greg Lester | EurekAlert!
Further information:
http://www.wistar.org

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 >>>