Recycling is important not only on a global scale, but also at the cellular level, since key molecules tend to be available in limited numbers. This means a cell needs to have efficient recycling mechanisms.
Researchers at the European Molecular Biology Laboratory (EMBL) and Heidelberg University, Germany, have now uncovered the first step in the recycling of a crucial molecular tag which ensures the instructions encoded in our genes are correctly carried out. The study, published this week in the journal Cell, sheds new light on a proof-reading process that helps protect us from genetic diseases.
The translation of information from gene to protein in our cells is very important, but also error-prone. As errors can lead to diseases, several control mechanisms check for mistakes along the way. One such mechanism, called nonsense-mediated decay (NMD), is based on a molecular tag that is attached to messenger RNAs, an intermediate step in the translation from DNA to protein. The tag, called exon-junction complex (EJC), tells the NMD machinery if an RNA is faulty, potentially dangerous and should be degraded. Overall, a cell would need to mark around 400,000 sites with EJCs, but it only has 10,000 copies of one of the marker's components. This means EJCs must be broken down as soon as possible, so that their components can be re-used.
Researchers in the groups of Matthias Hentze, associate director of EMBL, and Andreas Kulozik at the University Clinic Heidelberg discovered that a protein called PYM is responsible for the disassembly and recycling of EJCs.
“Our results were very surprising,” says Niels Gehring, who carried out the research. “Everybody had assumed that ribosomes, the large structures that carry out protein assembly, simply iron out the EJCs as they pass. Now we see that this is not quite right, because without PYM EJC disassembly is impaired.”
Although PYM can be found on its own in the cell, it tends to associate with ribosomes. This explains why - and how - EJCs are removed when the ribosome goes by, and could also ensure that they are not removed too early. If that happened, NMD would be compromised, as the proofreading machinery would have no markers to guide it. This in turn could have wider consequences, as NMD influences how diseases such as thalassaemia, Duchenne's muscular dystrophy and cystic fibrosis manifest themselves.
“The new insights fill an important gap in the basic understanding of a vital cellular process,” says Hentze. “But they also have medical implications. Ultimately we would like to find ways to modulate NMD pharmacologically to influence the development and course of genetic diseases.”
The research was conducted in the joint Molecular Medicine Partnership Unit (MMPU), a collaboration between EMBL and Heidelberg University. “The MMPU bridges the gap between basic and clinical research. The constant cross-fertilisation between biologists and medical scientists guides our studies and often leads to discoveries that are applicable to medicine,” says Kulozik, medical director and professor of pediatrics at Heidelberg University.
Anna-Lynn Wegener | EMBL
Further reports about: > EJC > EMBL > MMPU > Molecular Biology > Molecular Target > NMD > PYM > RNA > Recycler > cystic fibrosis > efficient recycling mechanisms > error-prone > genetic disease > genetic disorders > key molecules > muscular dystrophy > protein recycling mechanism > ribosomes > thalassaemia
Are there sustainable solutions in dealing with dwindling phosphorus resources?
16.10.2017 | Leibniz-Institut für Nutzierbiologie (FBN)
Strange undertakings: ant queens bury dead to prevent disease
13.10.2017 | Institute of Science and Technology Austria
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
It's possible to produce hydrogen to power fuel cells by extracting the gas from seawater, but the electricity required to do it makes the process costly. UCF...
Mercury, our smallest planetary neighbor, has very little to call an atmosphere, but it does have a strange weather pattern: morning micro-meteor showers.
Recent modeling along with previously published results from NASA's MESSENGER spacecraft -- short for Mercury Surface, Space Environment, Geochemistry and...
10.10.2017 | Event News
10.10.2017 | Event News
28.09.2017 | Event News
16.10.2017 | Physics and Astronomy
16.10.2017 | Earth Sciences
16.10.2017 | Physics and Astronomy