Our genes decide about many things in our lives – what we look like, which talents we have, or what kind of diseases we develop. For a long time dismissed as “junk DNA”, we now know that also the regions between the genes fulfil vital functions. They contain a complex control machinery with thousands of molecular switches that regulate the activity of our genes. Until now, however, regulatory DNA regions have been hard to find. Scientists around Patrick Cramer at the Max Planck Institute (MPI) for Biophysical Chemistry in Göttingen and Julien Gagneur at the Technical University of Munich (TUM) have now developed a method to find regulatory DNA regions which are active and controlling genes.
The genes in our DNA contain detailed assembly instructions for proteins, the “workers” carrying out and controlling virtually all processes in our cells. To ensure that each protein fulfils its tasks at the right time in the right place of our body, the activity of the corresponding gene has to be tightly controlled.
This function is taken over by regulatory DNA regions between the genes, which act as a complex control machinery. “Regulatory DNA regions are essential for development in humans, tissue preservation, and the immune response, among others,” explains Patrick Cramer, head of the Department for Molecular Biology at the MPI for Biophysical Chemistry. “Furthermore, they play an important role in various diseases. For example, patients suffering from cancer or cardiovascular conditions show many mutations in exactly those DNA regions,” the biochemist says.
When regulatory DNA regions are active, they are first copied into RNA. “The resulting RNA molecules have a great disadvantage for us researchers though: The cell rapidly degrades them, thus they were hard to find until now,” reports Julien Gagneur, who recently moved with this group from the Gene Center of the Ludwig-Maximilians-Universität Munich to the TUM. “But exactly those short-lived RNA molecules often act as vital molecular switches that specifically activate genes needed in a certain place of our body. Without these molecular switches, our genes would not be functional.”
An anchor for short-lived molecular switches
Björn Schwalb and Margaux Michel, members of Cramer’s team, as well as Benedikt Zacher, scientist in Gagneur’s group, have now succeeded in developing a highly sensitive method to catch and identify even very short-lived RNA molecules – the so-called TT-Seq (transient transcriptome sequencing) method. The results are reported in the latest issue of the renowned scientific journal Science on June 3rd.
In order to catch the RNA molecules, the three junior researchers used a trick: They supplied cells with a molecule acting as a kind of anchor for a couple of minutes. The cells subsequently incorporated the anchor into each RNA they made during the course of the experiment. With the help of the anchor, the scientists were eventually able to fish the short-lived RNA molecules out of the cell and examine them.
“The RNA molecules we caught with the TT-Seq method provide a snapshot of all DNA regions that were active in the cell at a certain time – the genes as well as the regulatory regions between genes that were so hard to find until now,” Cramer explains. “With TT-Seq we now have a suitable tool to learn more about how genes are controlled in different cell types and how gene regulatory programs work,” Gagneur adds.
In many cases, researchers have a pretty good idea which genes play a role in a certain disease, but do not know which molecular switches are involved. The scientists around Cramer and Gagneur are hoping to be able to use the new method to uncover key mechanisms that play a role during the emergence or course of a disease. In a next step they want to apply their technique to blood cells to better understand the progress of a HIV infection in patients suffering from AIDS.
Björn Schwalb, Margaux Michel, Benedikt Zacher, Katja Frühauf, Carina Demel, Achim Tresch, Julien Gagneur, Patrick Cramer: TT-Seq maps the human transient transcriptome.
Science 352,1225-1228 (2016), doi: 10.1126/science.aad9841.
Prof. Dr. Patrick Cramer, Department of Molecular Biology
Max Planck Institute for Biophysical Chemistry, Göttingen
Phone: +49 551 201-2800
Prof. Dr. Julien Gagneur, Computational Biology Group
Technical University of Munich
Phone: +49 89 289-19411
Dr. Anne Morbach, Public Relations Office
Max Planck Institute for Biophysical Chemistry, Göttingen
Phone: +49 551 201-1308
http://www.mpibpc.mpg.de/15377790/pr_1620 – original press release
http://www.mpibpc.mpg.de/cramer – Website of the Department of Molecular Biology at the Max Planck Institute for Biophysical Chemistry, Göttingen
http://www.gagneurlab.in.tum.de – Website of the Computational Biology Group at the Technical University of Munich
Dr. Carmen Rotte | Max-Planck-Institut für biophysikalische Chemie
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
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...
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:...
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...
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...
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...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine