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| Heidelberg, 16 May 2007 |
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| Mechanism of microRNAs deciphered
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Researchers discover how microRNAs block protein synthesis
Press
Release 16 May 2007 [PDF]
Over 30% of our genes are under
the control of small molecules called microRNAs. They prevent
specific genes from being turned into protein and regulate
many crucial processes like cell division and development,
but how they do so has remained unclear. Now researchers
from the European Molecular Biology Laboratory [EMBL]
have developed a new method that uncovered the mode of
action of microRNAs in a test tube. The study, which is published
in the current online issue of Nature, reveals that
microRNAs block the initiation of translation, the earliest step
in the process that turns genetic information stored on messenger
RNAs into proteins.
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.
Source Article
R. Thermann & M.W. Hentze. Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation, Nature online, 16 May
2007
Press Contact
Anna-Lynn Wegener
Press Officer
EMBL Heidelberg
Tel: +49 6221 387-8452
Email: wegener@embl.de |
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