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.
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!
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
Pollen taxi for bacteria
18.07.2018 | Technische Universität München
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
18.07.2018 | Life Sciences
18.07.2018 | Materials Sciences
18.07.2018 | Health and Medicine