Before a cell divides, it must duplicate all its components. To boost the production of the various proteins that are required for this, their blueprints, the genes, have to be read at increased levels. Thus, many messenger RNA (mRNA) molecules are formed and are subsequently translated into proteins in the protein factories of the cell known as ribosomes. On this level, the protein production may be further fuelled by increasing the levels of mRNA translation. Special proteins that promote the binding of the mRNA to the ribosome play an important role in this process. “For some time now, we have suspected MCT-1 to be a candidate for this role,” says Aurelio Teleman, department head at the DKFZ, “because it binds mRNA and is found with particularly high frequency in leukemia cells, which divide very rapidly.” However, up to now the exact mechanism by which it accomplishes this task had remained in the dark.
Sibylle Schleich, first author of the article, found out in studies on fruit flies (Drosophila) that MCT-1 teams up with a partner called DENR to make particular mRNA molecules stay bound to the ribosome long enough to facilitate their translation into proteins. The mRNAs for proteins that are required for cell division – and which are therefore also involved in cancer – particularly depend on the assistance by the MCT-1-DENR couple. “Without the help from the MCT-1-DENR complex, these mRNAs drop off from the ribosome after a short time and are not translated into protein,” Schleich explains. Flies whose cells lacked either MCT-1 or DENR did not develop beyond the pupal stage and were not viable afterwards. “So we have discovered a universal control mechanism of the cell that affects the total production of proteins that are relevant for cell division,” says Aurelio Teleman, explaining the relevance of this work. Teleman and his co-workers have also found the MCT1-DENR complex in human cells. This means that it might represent an interesting target for new anti-cancer drugs.
Sibylle Schleich, Katrin Strassburger, Philipp Christoph Janiesch, Tatyana Koledachkina, Katharine K. Miller, Katharina Haneke, Yong-Sheng Cheng, Katrin Kuechler, Georg Stoecklin, Kent E. Duncan and Aurelio A. Teleman “DENR•MCT-1 Promotes Translation Reinitiation Downstream of uORFs to Control Tissue Growth“, Nature, 13401, DOI: 10.1038/nature13401
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.