Decifrado el mecanismo de los microARNsContributed by: Anonymous · Views: 911
Contributed by: Anonymous · May 17, 2007 @ 12:59 PM MDT · Views: 911
Mechanism of microRNAs deciphered
Researchers discover how microRNAs block protein synthesis
The central dogma in molecular biology says that the genetic information stored as DNA is transcribed into molecules of messenger RNAs, which are then translated into proteins. MicroRNAs are small molecules that do not encode proteins themselves but bind to messenger RNAs that do. They function as locks for messenger RNAs and prevent their translation into proteins, but how they bring about this effect and at which stage of protein synthesis they interfere is a long-standing puzzle.
"So far it has been impossible to directly examine how and when microRNAs lock up messenger RNAs," says Matthias Hentze, Associate Director of EMBL, "because until now all we could look at were messenger RNAs that had already been locked up within cells. To investigate the locking process itself, we developed a test tube system that recreates close to real life conditions of fruitfly embryos. Adding messenger RNAs to this system we could monitor for the first time how they got locked up by microRNAs."
Applying this new system, Rolf Thermann, who carried out the research in Hentze's lab, discovered that miR2, an important microRNA in fruit flies, blocks translation very early on, even before the cellular machinery needed can assemble. Bound by miR2, a messenger RNA molecule is no longer accessible to ribosomes, the complexes that carry out protein synthesis.
"Strikingly, the messenger RNA locked up in this way looks very similar to a messenger RNA that undergoes translation," Thermann says. "It is bound by big microRNA complexes that strongly resemble ribosomes, but they are not. This explains why when looking at already locked up messenger RNA many scientists thought that translation had already started and microRNAs must interfere at a later stage of the process. It will be exciting to determine what these complexes are made of and how exactly they function."
The new approach to studying micro RNAs in action in a test tube may pave the way to similar studies of human and other microRNAs. MicroRNAs play an important role in various diseases including cancer, diabetes and viral infections. The new in vitro system will not only help shed light on the role of microRNAs in disease, but could also serve as a basis for new methods of drug discovery.
R. Thermann & M.W. Hentze. Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation, Nature online, 16 May 2007
Credits: European Molecular Biology Laboratory (EMBL)