From Gene to Protein – New Insights of MDC Researchers
The Berlin
Institute for Medical Systems Biology (BIMSB) was launched by the MDC in 2008,
supported by start-up funding from the Federal Ministry of Education and
Research (BMBF) and the Senate of Berlin. The focus of Medical Systems Biology is
not on genes and their proteins as isolated components, but on their regulation
and their interaction with each other and on their relevance for disease
processes. Since its inception, the internationally renowned BIMSB has become a
beacon in the Berlin research landscape. It works closely with other
institutions in numerous research networks and participates in excellence
clusters with the Berlin universities, collaborating in particular with
Humboldt University and Charité – Universitätsmedizin
Berlin and also with New York University.
Proteins
are the major building blocks of life. “They control virtually all biological
processes ranging from heartbeat and oxygen transport up to and including
thinking,” Matthias Selbach explained. The blueprint
for proteins is stored in the genes in the cell nucleus. The messenger RNA
(mRNA) formed in the cell nucleus (transcription) brings a copy of the
blueprint to the protein factories of the cell in the cytoplasm, to the
ribosomes. There the information of the mRNAs is used for protein production
(translation). The fundamental question was which of the two processes, i.e.
transcription or translation, plays the dominant role in regulating cellular
protein levels.
The
starting point of the MDC researchers was to measure the turnover of cellular
mRNAs and proteins and mRNA and protein levels. They used high-throughput
technologies such as quantitative mass spectrometry and the latest sequencing
techniques, which are available close by at the MDC / BIMSB. In total, they quantified
proteins and mRNAs for more than 5,000 genes. By means of mathematical
modeling, the researchers drew conclusions from the collected data about the
control of protein levels. Intriguingly, they
observed that cellular protein levels mainly depend on translation of mRNAs in the protein factories of the cytoplasm. “The ribosomes ultimately determine protein abundance. Some mRNAs are
translated into only one protein per hour, others are translated 200 times,”
Matthias Selbach said.
Cells work in an energy-efficient way
Furthermore,
the researchers found that cells use their resources very efficiently. Most
mRNAs and proteins of abundantly expressed housekeeping genes (these genes
maintain the normal operations of the body) are very stable. In this way the
cell saves valuable energy, because protein production consumes many resources.
In contrast, proteins responsible for rapid signaling processes are typically
unstable. Cells can therefore quickly adapt to changes in their surroundings. This may
also explain why the decisive control step takes place in the cytoplasm and not
in the nucleus. Since it constitutes the last step in the production chain,
this allows cells to respond dynamically to their environment.
The researchers hope their results will also be
relevant for diseases. "So far, this is purely basic research,” Matthias Selbach stressed. "But we also know that the
production of proteins is disturbed in many diseases, for example cancer."
Very little is known about where the process gets out of control. Until now,
researchers focused almost exclusively on the nucleus to find answers to this
question. The new findings, however, show that the protein factories in the
cytoplasm are of great significance. Perhaps this is where the key to understanding
diseases can be found.
*Global quantification of mammalian gene expression control
Björn Schwanhäusser1, Dorothea
Busse1, Na Li1, Gunnar Dittmar1, Johannes
Schuchhardt2, Jana Wolf1, Wei Chen1 &
Matthias Selbach1
1Max Delbrück Center
for Molecular Medicine, Robert-Rössle-Str. 10,
D-13092 Berlin, Germany. 2MicroDiscovery GmbH, Marienburger
Str. 1, D-10405 Berlin, Germany.
Barbara Bachtler
Press Department
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Member of the Helmholtz Association
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de
http://www.mdc-berlin.de/
