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 How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH

nachricht A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can we see monkeys from space? Emerging technologies to map biodiversity

An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.

Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...

Im Focus: Climate satellite: Tracking methane with robust laser technology

Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.

Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...

Im Focus: How protons move through a fuel cell

Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.

As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...

Im Focus: A unique data centre for cosmological simulations

Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.

With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...

Im Focus: Scientists develop molecular thermometer for contactless measurement using infrared light

Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine

Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Plants are networkers

19.06.2017 | Event News

Digital Survival Training for Executives

13.06.2017 | Event News

Global Learning Council Summit 2017

13.06.2017 | Event News

 
Latest News

Quantum thermometer or optical refrigerator?

23.06.2017 | Physics and Astronomy

A 100-year-old physics problem has been solved at EPFL

23.06.2017 | Physics and Astronomy

Equipping form with function

23.06.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>