> The results appear in the most recent issue of Nature Structural and Molecular Biology.
Researchers at the University of Pennsylvania School of Medicine have discovered a unique molecular pathway that detects and selectively eliminates defective messenger RNAs from red blood cells. Other such pathways – known as surveillance pathways – operate in a more general way, in many cell types. Knowing how this specific surveillance system works can help researchers better understand hereditary diseases, in this case, thalassemia, a form of anemia, which is the most common genetic disorder worldwide.
The results appear in the most recent issue of Nature Structural and Molecular Biology.
Cells have developed surveillance mechanisms that identify and destroy abnormal RNAs. Mistakes in a cell’s reading of RNA into protein can lead to the production of an abnormal protein, and this can result in abnormal cell function or death.
The form of thalassemia studied by the Penn group is caused by a mutation that allows the cell’s ribosome to read too far, making a protein that is too long. Thalassemias result from an underproduction of hemoglobin proteins – the oxygen carrying molecule in blood – hence the anemia. The particular mutation they study is carried by millions of people in Southeast Asia and is a major a cause of fetal loss and disease in adults. Specifically in this study they show how far the ribosome has to read into the RNA to trigger mRNA destabilization.
Several surveillance pathways have been identified over the last few years that recognize specific types of mutations in RNAs. For example, the most well-described pathway is one that recognizes nonsense mutations that result in an RNA that makes a protein that is too short. Duchenne's muscular dystrophy and cystic fibrosis are examples of hereditary diseases that result from nonsense mutations.
“We describe a surveillance pathway that targets RNA that is only found in red blood cells,” says senior author Stephen A. Liebhaber, MD, Professor of Genetics and Medicine. “More general surveillance pathways are in all cells. The specificity of this particular surveillance pathway has not been previously observed and predicts that there’s something quite unusual about how RNAs are handled in red blood cells. We’re interested in how this specific surveillance system works in red blood cells because such understanding will increase our knowledge of how these cells make high levels of hemoglobin and how defects in this system could contribute to genetic disorders and possibly be reversed.”
“This type of surveillance pathway that is regulated at the tissue level could also exist in other highly specialized cells,” says first author Jian Kong, PhD, Senior Research Investigator. “Investigating the mechanism of this pathway may help in understanding a wider range of genetic disorders.”
Liebhaber is looking forward to further analysis of this surveillance pathway in order to determine why it is specific to red cells and to define the corresponding steps in gene expression in the red cell that are so unusual. Such information should lead to new ideas on how to manipulate this system in a variety of blood diseases.
The research was funded by the National Heart, Lung, and Blood Disease Institute.
Karen Kreeger | EurekAlert!
How brains surrender to sleep
23.06.2017 | IMP - Forschungsinstitut für Molekulare Pathologie GmbH
A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)
An international team of scientists has proposed a new multi-disciplinary approach in which an array of new technologies will allow us to map biodiversity and the risks that wildlife is facing at the scale of whole landscapes. The findings are published in Nature Ecology and Evolution. This international research is led by the Kunming Institute of Zoology from China, University of East Anglia, University of Leicester and the Leibniz Institute for Zoo and Wildlife Research.
Using a combination of satellite and ground data, the team proposes that it is now possible to map biodiversity with an accuracy that has not been previously...
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
23.06.2017 | Physics and Astronomy
23.06.2017 | Physics and Astronomy
23.06.2017 | Information Technology