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| Heidelberg,
Thursday 25 August 2005 |
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| A double punch for female survival |
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| Predoctoral fellow Karsten Beckmann and Matthias Hentze. |
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![In order to create proteins, a ribosome must dock onto an mRNA molecule and scan the protein-encoding part [red]. Beckmann, Hentze and their colleagues discovered that two copies of a protein called SXL [green] attach themselves in different places and work together to block the activity of the ribosome in two different ways.](../../../../../images/press/press05/press25aug05pic2s.jpg) |
| In order to create proteins,
a ribosome must dock onto an mRNA molecule and scan
the protein-encoding part [red]. Beckmann, Hentze
and their colleagues discovered that two copies
of a protein called SXL [green] attach themselves
in different places and work together to block the
activity of the ribosome in two different ways. |
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Press
Release 25 August 2005 [PDF]
Achieving equality between the sexes can be a challenge
even for single cells. Since evolution began removing
bits of male DNA to create the 'Y' chromosome, males
have had a single copy of certain key genes on the
X chromosome, whereas females have two. Normally
this would lead females to produce twice the amount
of some proteins, which could be fatal, but cells
have developed ways to prevent this. Researchers
at the European Molecular Biology Laboratory [EMBL]
in Heidelberg have now made a breakthrough in understanding
how this balance, called 'dosage compensation,'
is maintained. They have discovered a unique double-locking
mechanism which prevents the production of a molecule
that would be fatal for female cells; their work
is reported in the current issue of Cell.
Genes are used to create mRNA molecules, which are
then used to create proteins. "Cells build a machine
called a ribosome on an mRNA to transform its information
into proteins," Hentze says. "We've known that a
protein in female flies called SXL can block the
work of this machine, but we didn't know how. This
study unravels how SXL prevents the synthesis of
another protein, called MSL-2, which is essential
in males but would kill female flies."
An mRNA molecule is linear, with a protein-encoding
part sandwiched in the middle between regulatory
regions near the head and the tail. Most research
has focused on interactions between the head region
and the ribosome, because it is here that cells
assemble a 'docking bridge' for the protein-synthesis
machinery. Scientists have discovered other cases
where protein synthesis is blocked at this head
region. But this case turned out to be different.
"Copies of SXL have to be attached to both ends
of the msl-2 mRNA to efficiently stop the synthesis
of MSL-2 proteins," says Karsten Beckmann, a PhD
student in Hentze's lab, who headed the current
project.
"To our surprise we found that
the SXL molecules bound at the two ends do not directly
work together, but that they help each other by
acting on two separate steps. The SXL that binds
to the tail of the mRNA blocks the construction
of the docking bridge for the ribosome at the head
end." The second copy of SXL has a different function,
he says. Single control mechanisms are often 'leaky',
which means that ribosomes may still succeed in
binding to the mRNA. These ribosomes have to be
stopped, and the extra copy of SXL at the head regulatory
region prevents them from negotiating their way
towards the proteinencoding region in the middle.
What's unusual is that SXL is serving as its own
'backup'. The work by Hentze and his colleagues
shows for the first time that a single regulatory
molecule can deliver a 'double punch' to lock away
the mRNA from the ribosome, thus preventing the
expression of otherwise fatal proteins.
"Some diseases
develop because of a disturbance in the fine-tuning
of protein dosages," Hentze says. "The control of
protein synthesis is also crucial in the growth
and development of animal tissues. Until a few years
ago, scientists thought this happened almost uniquely
at the level of genes. So it's exciting to find
an entirely new mechanism that evolved to let cells
take control at the level of RNA. No one knows how
widely this type of back-up mechanism is used. We're
now investigating some other contexts in which a
very similar mechanism might be at work."
Source Article A dual inhibitory mechanism restricts msl-2mRNA translation for dosage compensation in Drosophila
K. Beckmann, M. Grskovic, F. Gebauer and M. Hentze
Cell, 26 August 2005
Press Contact
Sarah Sherwood
EMBL Information Officer, European Molecular Biology Laboratory,
Meyerhofstrasse 1, 69117 Heidelberg, Germany
Tel: +49 [0] 6221 387125
E-mail: sarah.sherwood@embl.de |
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