Heidelberg biochemists identify detection signal for breaking down excess ribosomal RNA
A growing, dividing cell uses most of its energy store to make its “protein factories”, the ribosomes. An important player in their “assembly” is the exosome, a molecular shredding machine that breaks down excess ribonucleic acid (RNA).
Die schematische Darstellung zeigt, wie das Exosom die überschüssige RNA am entstehenden Ribosom degradiert. Daran beteiligt ist ein Adapterprotein am Prä-Ribosom, das eine Konsensus Erkennungssequenz (Barcode) trägt, an die das Mtr4 Helferprotein binden kann. Dadurch wird das Exosom an die Ziel-RNA dirigiert. Copyright: Universität Heidelberg
Researchers working with Prof. Dr. Ed Hurt at the Heidelberg University Biochemistry Center (BZH) have discovered how the exosome identifies its target RNA. The team identified a specific detection signal, comparable to a postal code or bar code that targets the exosome to the remote RNA. The results of the research were published in the journal “Cell”.
According to Prof. Hurt, the production of ribosomes is an extremely complex process that follows a strict blueprint with numerous quality-control checkpoints. The protein factories are made of numerous ribosomal proteins (r-proteins) and ribosomal ribonucleic acid (rRNA).
More than 200 helper proteins, known as ribosome biogenesis factors, are needed in the eukaryotic cells to correctly assemble the r-proteins and the different rRNAs. Three of the total of four different rRNAs are manufactured from a large precursor RNA. They need to be “trimmed” at specific points during the manufacturing process, and the superfluous pieces are discarded. “Because these processes are irreversible, a special check is needed,” explains Ed Hurt.
A substantial portion of this excess ribosomal RNA is broken down by the exosome, a molecular machine consisting of multiple protein subunits. Together they form a structure similar to a barrel, through which the RNA is channelled. The subunit of the exosome that degrades the RNA into its individual components, or nucleotides, sits at the end of this channel. “This process has already been well-described, but we still didn’t understand how the exosome detected its target RNA and distinguished it from the numerous RNA molecules that needed to remain intact,” explains Ed Hurt.
Matthias Thoms and Dr. Emma Thomson of Prof. Hurt’s research team have now been able to identify two ribosome biogenesis factors located near the target RNA on the unfinished ribosome that guide the exosome to its target. Both protein factors act during ribosome assembly, but operate at a different time and position.
Although the two proteins are structured differently, they do share one important characteristic. The Heidelberg researchers discovered both have a short signal sequence similar to a barcode or postal code. Through this detection signal, a helper protein of the exosome is recruited to point to the target RNA. The exosome is then able to start its task and shred the unneeded RNA.
Prof. Hurt’s team of scientists now want to identify other proteins with the described signal sequence to find out how the exosome is able to eliminate such a broad spectrum of different RNA. “The exosome is a universal protein complex that is essential in all cells for RNA homeostasis, that is, the equilibrium between RNA creation and degradation. We assume that the type of target RNA detection we discovered represents a general mechanism for exosome regulation,” explains Prof. Hurt.
“Our findings could also lead to a better molecular understanding of illnesses in which defects were identified in the exosome or their helper proteins.” This would establish the mutations in exosome components that could cause autoimmune diseases or multiple myeloma in humans.
M. Thoms, E. Thomson, J. Baßler, M. Gnädig, S. Griesel and E. Hurt: The Exosome Is Recruited to RNA Substrates Through Specific Adapter Proteins. Cell 162, 1029-1038 (27 August 2015), doi: 10.1016/j.cell.2015.07.060
Prof. Dr. Ed Hurt
Heidelberg University Biochemistry Center
Phone +49 6221 54-4781, -4173
Communications and Marketing
Press Office, phone +49 6221 54-2311
Marietta Fuhrmann-Koch | idw - Informationsdienst Wissenschaft
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration
"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...
Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.
Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
16.01.2017 | Trade Fair News
16.01.2017 | Automotive Engineering
16.01.2017 | Life Sciences