Messenger RNA molecules contain genetic information and thus control the synthesis of proteins in living cells. Biochemists at the University of Bayreuth and the University of Bonn have now discovered a way to regulate this process which is central to gene expression: Certain actinobacteria contain a protein that binds RNA molecules under blue light and can thereby deactivate them. In principle, it is thus possible to switch RNA-controlled protein synthesis on and off via light, not just in bacteria but also in mammalian and even human cells. The findings published in "Nature Chemical Biology" are the basis for a new field of research: optoribogenetics.
For some time now, light signals have been used to alter the transcription of genetic information - and consequently protein synthesis directed by RNA (Ribonucleic Acids) molecules - at the DNA level. This approach is part of optogenetics and is now a well-established method of molecular and cell biology.
However, the new study now shows for the first time a mechanism by which the interaction between RNA and specific proteins can be influenced by light. Gene expression in bacteria can hence be controlled directly at the level of RNA molecules.
The researchers led by Prof. Dr. Andreas Möglich in Bayreuth and Prof. Dr. Günter Mayer in Bonn have demonstrated that this mechanism can be transferred to mammalian cells. "Over the next few years, we will extend the light-controlled regulation to various cellular processes involving RNA.
The resulting tools, which have not been available to date, will greatly advance the investigation of central cellular processes. The foundation stone for optoribogenetics, a new complement to optogenetics, has now been laid," says Prof. Dr. Andreas Möglich.
Search for a candidate protein reacting to light
The starting point of the research work was the hunt for a bacterial photoreceptor protein able to change its own binding behaviour in relation to RNA under the influence of light. The scientists searched the existing sequence databases and found what they were looking for.
Bacteria of the species Nakamurella multipartita contain a protein with a conspicuous tripartite architecture: three different sections or “domains” called "PAS", "ANTAR" and "LOV", are arranged one after the other in an unusual sequence.
As could be shown in cooperation with the research group of Prof. Dr. Robert Bittl at Freie Universität Berlin, the LOV photosensor domain reacts to blue light and transmits the signals to the ANTAR domain. The ANTAR domain then changes its structure so that RNA molecules are bound and thus made inaccessible: They are no longer available for gene expression and the genetic information contained in them is no longer used for the synthesis of proteins.
Only when the blue light irradiation ceases, and the ANTAR domain returns to its normal structure, does the interaction with the RNA come to a halt. Now the RNA becomes active again. The researchers first established and demonstrated this process using RNA aptamers. These are small RNA molecules with a hairpin-like structure that can enter the structure of the ANTAR domain, which is opened under blue light, and are bound there. Mayer: "Aptamers work in modular fashion: They can be linked to other units like a building block system."
The scientists also tested their new research approach on eukaryotic cells into which they had previously introduced the bacterial protein and the RNA aptamers. In these cells, too, the structural changes triggered by blue light lead to messenger RNA molecules binding to the protein and, in this state, suspending gene expression. "We now have a light switch with which the cellular activity of different RNA molecules can be specifically switched on and off," explains Prof. Dr. Günter Mayer from the LIMES Institute at the University of Bonn.
His colleague from Bayreuth, Prof. Dr. Andreas Möglich, adds: "The approach to light-regulated control can in principle be transferred to numerous other RNA-based processes, such as the processing of micro-RNAs and the associated phenomenon of gene silencing.” In subsequent studies, the two scientists and their research groups hope to investigate the extent to which the newly discovered mechanism can be used in model organisms to control gene expression and other processes.
Embargo: Please do not publish before August 26th 2019 - 5 p.m.!
Prof. Dr. Andreas Möglich
University of Bayreuth
Phone: +49 (0)921 – 7835
Prof. Dr. Günter Mayer
University of Bonn
Phone: +49 (0)228-734808
Anna M. Weber et al.: A blue light receptor that mediates RNA binding and translational regulation. Nature Chemical Biology, DOI: 10.1038/s41589-019-0346-y.
Anja-Maria Meister | idw - Informationsdienst Wissenschaft
Too much of a good thing: overactive immune cells trigger inflammation
16.09.2019 | Universität Basel
The sleep neuron in threadworms is also a stop neuron
16.09.2019 | Goethe-Universität Frankfurt am Main
Later during this century, around 2060, a paradigm shift in global energy consumption is expected: we will spend more energy for cooling than for heating....
Researchers from the Department of Atomically Resolved Dynamics of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg, the University of Potsdam (both in Germany) and the University of Toronto (Canada) have pieced together a detailed time-lapse movie revealing all the major steps during the catalytic cycle of an enzyme. Surprisingly, the communication between the protein units is accomplished via a water-network akin to a string telephone. This communication is aligned with a ‘breathing’ motion, that is the expansion and contraction of the protein.
This time-lapse sequence of structures reveals dynamic motions as a fundamental element in the molecular foundations of biology.
Two research teams have succeeded simultaneously in measuring the long-sought Thorium nuclear transition, which enables extremely precise nuclear clocks. TU Wien (Vienna) is part of both teams.
If you want to build the most accurate clock in the world, you need something that "ticks" very fast and extremely precise. In an atomic clock, electrons are...
Researchers from Chalmers University of Technology have demonstrated a detector made from graphene that could revolutionize the sensors used in next-generation space telescopes. The findings were recently published in the scientific journal Nature Astronomy.
Beyond superconductors, there are few materials that can fulfill the requirements needed for making ultra-sensitive and fast terahertz (THz) detectors for...
A supersolid is a state of matter that can be described in simplified terms as being solid and liquid at the same time. In recent years, extensive efforts have been devoted to the detection of this exotic quantum matter. A research team led by Tilman Pfau and Tim Langen at the 5th Institute of Physics of the University of Stuttgart has succeeded in proving experimentally that the long-sought supersolid state of matter exists. The researchers report their results in Nature magazine.
In our everyday lives, we are familiar with matter existing in three different states: solid, liquid, or gas. However, if matter is cooled down to extremely...
10.09.2019 | Event News
04.09.2019 | Event News
29.08.2019 | Event News
16.09.2019 | Life Sciences
16.09.2019 | Materials Sciences
16.09.2019 | Health and Medicine