Discovering how blood cells develop
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
http://www.mdc-berlin.de/englisch/about_the_mdc/public_relations/e_index.htm
