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Marking the landing site –

The protein complex Prp19 plays multiple roles in gene expression

Munich, 05/16/2011

The hereditary information stored in the DNA is utilized primarily to specify the structures of a different class of molecules – proteins, and the implementation of the genetic program is a highly complex process. In higher organisms, the DNA resides in the cell nucleus, while protein synthesis takes place in the cytoplasm, with messenger RNA (mRNA) forming the link between the two. The mRNAs are copied from defined tracts of the DNA and then exported to the cytoplasm, where they are translated into the corresponding proteins. The TREX complex is known to play a crucial role in coupling gene transcription to mRNA export, but it was hitherto unclear how TREX is directed to DNA sequences that are being actively transcribed. A research team led biologist Dr. Katja Sträßer, who is based at LMU’s Genzentrum, has now identified a first factor that is required for this task – the protein complex Prp19. Prp19 was already known to participate in the processing of RNA molecules that accompanies their transcription, so it is obviously well placed to serve a second function as a recruiting factor for TREX. (Genes & Development, May 2011)

Long double-stranded molecules of DNA form the basis of the chromosomes in the cell nucleus and encode the instructions for the synthesis of proteins, the cell’s machine tools. The genetic information in the DNA is first transcribed into single-stranded mRNA molecules, which are then exported to program protein synthesis in the cytoplasm. This entire process is referred to as gene expression, and its various component steps have been extensively studied. However, as Sträßer points out, “The different steps are not isolated events, but are intimately connected.” One of the connections is provided by the TREX complex, which links the transcription step to the export of the newly synthesized mRNA from the nucleus. TREX interacts with the transcription machinery and also recruits proteins that are required for the export of mRNAs to the cytoplasm. The dissection of TREX function is a primary goal of Sträßer’s research. TREX is found in all eukaryotic cells, from single-celled organisms to humans, and this high degree of evolutionary conservation is a measure of its functional importance. “Up to now, it has been completely unclear how the TREX complex is recruited to actively transcribed genes,” says Sträßer. Now Sträßer and her team identified the first factor that mediates the recruitment of TREX to actively transcribed genes. To their surprise, this turned out to be the protein complex Prp19 that was previously only known for its function in the processing of newly synthesized RNAs. Processing is necessary because the primary RNA transcript often contains internal stretches that are not required to specify protein structure and must be removed. In its newly discovered role as a landing light for TREX, Prp19 has been shown to interact directly with TREX as well as with the enzyme RNA polymerase II, which catalyzes mRNA synthesis. Prp19 is essential for the docking of TREX to active genes, which in turn is necessary for efficient transcription. For Katja Sträßer, the next step is to determine how exactly TREX and Prp19 interact.“There are still many open questions to be answered,” she says. (göd/PH))

The project was carried out under the auspices of the Center for Integrated Protein Science Munich (CiPSM) and supported by the Deutsche Forschungsgemeinschaft (DFG) as part of Priority Program (SFB) 646.

 

Publication:
"The Prp19 complex is a novel transcription elongation factor required for TREX occupancy at transcribed genes"
S. Chanarat, M. Seizl, K. Sträßer
Genes & Development, May 2011.
doi: 10.1101/gad.623411

 

Contact:
Dr. Katja Sträßer
GeneCenter LMU
Phone: +49 (0) 89 / 2180 – 76937
Email: strasser@lmb.uni-muenchen.de

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