A Macromolecular Shredder for RNA
Max Planck Researchers unravel the structure of the machinery for RNA disposal
Much in the same way as we use shredders to destroy documents that are no longer useful or that contain potentially damaging information, cells use molecular machines to degrade unwanted or defective macromolecules.
The crystal structure of a complete eukaryotic RNA Exosome complex reveals how it recognizes and processes its substrate. RNA (black) is recognized and unwound by the cap proteins (yellow, beige, orange), threaded inside the barrel (grey) and targeted to the active site of the catalytic subunit (in violet), where processive degradation occurs.
Graphics: Debora L. Makino/Copyright: MPI of Biochemistry
Scientists of the MPI of Biochemistry have now decoded the structure and the operating mechanism of the Exosome, a macromolecular machine responsible for degradation of ribonucleic acids (RNAs) in eukaryotes.
One of the functions of RNAs is to permit translation of the genomic information into proteins. The results of the studies now published in Nature show that the structural architecture and the main operation mode of the Exosome are conserved in all domains of life.
Any errors that occur during the synthesis of RNA molecules or unwanted accumulation of RNAs can be damaging to the cell. The elimination of defective RNAs or of RNAs that are no longer needed are therefore key steps in the metabolism of a cell. The Exosome, a multi-protein complex, is a key machine that shreds RNA into pieces. In addition, the Exosome also processes certain RNA molecules into their mature form. However, the molecular mechanism of how the Exosome performs these functions has been elusive.
A ubiquitous molecular shredder
Debora Makino, a postdoctoral researcher in the Research Department led by Elena Conti has now obtained an atomic resolution picture of the complete eukaryotic Exosome complex bound to an RNA molecule. The structure of this complex allowed the scientists to understand how the Exosome works.
“It is quite an elaborate machine: the Exosome complex forms a hollow barrel formed by nine different proteins through which RNA molecules are threaded to reach a tenth protein, the catalytic subunit that then shreds the RNA into pieces,” says Debora Makino. The barrel is essential for this process because it helps to unwind the RNA and prepares it for shredding. “Cells lacking any of the ten proteins do not survive and this shows that not only the catalytic subunit but also the entire barrel is critical for the function of the Exosome,” Makino explains.
The RNA-binding and threading mechanism used by the Exosome in eukaryotes is very similar to that of the Exosome in bacteria and archaebacteria that the researchers had structurally characterized in earlier studies. “Although the chemistry of the shredding reaction in eukaryotes is very different from that used in bacteria and archaebacteria, the channeling mechanism of the Exosome is conserved, and conceptually similar to the channeling mechanism used by the Proteasome, a complex for shredding proteins,” says Elena Conti.
In the future, the researchers want to understand how the Exosome is selectively targeted by the RNAs earmarked for degradation and how it is regulated in the different cellular compartments.
Anja Konschak | Max-Planck-Institut
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...