No. 3/April 16, 2003
Discovering how blood cells develop
MDC researchers investigate key molecular pathways
One of the fundamental processes of biology is the conversion
of information encoded by genes into proteins, the universal building blocks
and driving force of life. Initially, the genetic information stored in DNA is
copied into transportable messenger-RNA (mRNA). mRNAs pass the information on
to ribosomes, the protein factories in cells. The latter assemble the proteins
from a series of individual building blocks, so-called amino acids, using the
mRNA as a template. The transmission of information from messenger-RNA into
specific sequences of amino acids is termed „translation“. For the majority of
genes, however, the individual steps controlling translation have remained a
mystery. Dr. Cornelis F. Calkhoven and Dr. Christine Müller from the research
group headed by Dr. Achim Leutz of the Max-Delbrück-Center for Molecular
Medicine (MDC) Berlin-Buch, in collaboration with researchers from the Clinical
Research Institute in Montreal/Canada, have now unraveled a novel regulatory
mechanism for translation which plays a key role in the formation of a variety
of blood cells. Their investigations have now been published in the renowned scientific
journal Genes and Development (Vol. 17, No. 8, April 15, 2003)*.
Dr. Calkhoven and his colleagues have been investigating a gene named scl. This gene plays a critical role in the early processes of blood formation. Mice deficient in this gene are unable to generate blood and consequently die. In humans, alterations in the scl gene can trigger T-cell leukemia.
Even though the scl-mRNA is a complete copy of the DNA encoded information, under certain physiological conditions only parts of the mRNA code is translated into proteins. This leads to the generation of SCL proteins of varying lengths. Depending on the ratio of the different SCL-protein forms, immature blood cells may develop either into blood platelets (called megakaryocytes or thrombocytes – involved in blood coagulation) or into red blood cells (erythrocytes – carrying oxygen around the body). The researchers have now been able to show that platelet formation requires the complete scl-information, while the development of red blood cells is based on the shorter versions of SCL.
What tells ribosomes which protein should be produced? Ribosomes get the starting signal for protein synthesis through certain factors. The type of blood cells that are produced may be directly dependent on the regulation of these factors. The researchers believe that the fine tune of this molecular switch is of great importance for blood formation. False regulation of this process may lead to the development of certain leukemias such as acute myeloid leukemia and megakaryocytic leukemia associated with Down’s syndrome.
*Translational
control of SCL isoform expression in hematopoietic lineage choice Cornelis F. Calkhoven 1,3,
Christine Müller 1,3, Richard Martin 2, Goradz Krosl 2,
Hubertus Pietsch 1, Trang Hoang 2, and Achim Leutz 1,4 3 These authors contributed
equally to this work 1 Max Delbrück Center for
Molecular Medicine (MDC) Berlin-Buch, Robert Roessle Str. 10, 13092 Berlin,
Germany, 2 Laboratory of Hemopoiesis and
Leukemia, Clinical Research Institute of Montreal 110, Pine Avenue West.
Montreal , Quebec H2W IR7 4 Corresponding author:e-mail aleutz@mdc-berlin.de ; Fax:+49/30 94 06
– 32 98
Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
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
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