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Structural Biology

Take the mRNA train

Messenger RNAs bearing the genetic information for the synthesis of proteins are delivered to defined sites in the cell cytoplasm by molecular motors. Researchers at the Helmholtz Zentrum München and their colleagues at the Ludwig-Maximilians-Universität München (LMU) have elucidated how the motors recognize their mRNA freight. The new findings appeared in the journal ‘Nature Structural & Molecular Biology’.


Schematic depiction of the binding of the protein She2p to RNA (magenta). Source: LMU, Dirk Niessing

Messenger RNAs carry the information for the assembly of proteins from the DNA in the cell nucleus to the sites of protein synthesis in the cytoplasm, and are crucial for cell function. In nerve cells, which form cytoplasmic processes that can be very long, many neuronal mRNAs must be conveyed to the sites of action of their protein products to ensure that the correct intercellular connections can be established. This requires a dedicated transport system that links remote regions of the cytoplasm with the cell nucleus. Dierk Niessing, leader of a research group in the Institute of Structural Biology (STB) at the Helmholtz Zentrum München and a professor at LMU’s Biomedical Center, has now characterized the structure of a macromolecular complex involved in the transport of mRNAs in yeast cells.

As a member of the DFG Research Unit “Macromolecular Complexes in mRNA Localization” Niessing explores the workings of the cell’s molecular transport systems in several model organisms. In the new study, carried out in collaboration with first author Franziska Edelmann, PhD student at the STB, the authors used baker’s yeast (Saccharomyces cerevisiae) to investigate at high resolution the succession of structural interactions required for the specific recognition of mRNA in the nucleus and its subsequent transport in the cytoplasm.

The research team systematically isolated and crystallized sub-complexes of the molecular machine responsible for the process and subjected them to X-ray crystallographic analysis. The resulting models clearly show, for the first time, how the hairpin-like conformation of the RNA is altered when it is recognized by the requisite binding proteins in the nucleus. “We were surprised to see that the RNA is not only recognized by these proteins, they also force it to adopt a new form. They staple it together, so to speak,” Niessing says. Carriage of the RNAs is the responsibility of so-called motor proteins. With the help of unfolded adaptor proteins, they attach to the RNA-protein complex as it emerges from the nucleus. In doing so, they stabilize the whole assembly, as the structural models demonstrate, thus allowing the RNA to be transported to its destination along the fibers that make up the cytoskeleton, which serve as the system’s ‘railway lines’.

The new data represent a major advance in our understanding of the transport of RNA – a process that is common to all organisms whose cells are nucleated and is vital for their survival. 

Further Information

Original Publication:
Edelmann, F.T. et al. (2017): Molecular architecture and dynamics of ASH1 mRNA recognition by its mRNA-transport complex. Nature Structural & Molecular Biology, DOI: 10.1038/nsmb.3351

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members.

The Institute for Structural Biology (STB) investigates the spatial structures of biological macromolecules, their molecular interactions and dynamics using integrated structural biology by combining X-ray crystallography, NMR-spectroscopy and other methods. Researchers at STB also develop NMR spectroscopy methods for these studies. The goal is to unravel the structural and molecular mechanisms underlying biological function and their impairment in disease. The structural information is used for the rational design and development of small molecular inhibitors in combination with chemical biology approaches.

As one of Europe's leading research universities, LMU Munich is committed to the highest international standards of excellence in research and teaching. Building on its 500-year-tradition of scholarship, LMU covers a broad spectrum of disciplines, ranging from the humanities and cultural studies through law, economics and social studies to medicine and the sciences. 15 percent of LMU‘s 50,000 students come from abroad, originating from 130 countries worldwide. The know-how and creativity of LMU's academics form the foundation of the University's outstanding research record. This is also reflected in LMU‘s designation of as a "university of excellence" in the context of the Excellence Initiative, a nationwide competition to promote top-level university research.