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
Ambush in a petri dish
24.11.2017 | Friedrich-Schiller-Universität Jena
Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology
High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons
The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
24.11.2017 | Physics and Astronomy
24.11.2017 | Health and Medicine
24.11.2017 | Earth Sciences