New DFG Research Unit
LMU will serve as the host institution for a newly constituted DFG Research Unit devoted to the study of the molecular processes responsible for the intracellular transport and localization of messenger RNAs.
Every aspect of the behavior of living cells is ultimately dependent on readout of the genetic information stored in the cell’s DNA. This process involves the “transcription” of specific segments of the genome into molecules of messenger RNA. Following export of the transcribed RNA molecules from the cell nucleus, where the genomic DNA resides, into the cytoplasm, the mRNAs are used to direct the synthesis of the proteins required for the functions appropriate to each cell type. In many cases, this also requires the delivery of the appropriate mRNAs to the sites of action of their protein products. This last operation – generally referred to as ‘mRNA localization’ – is the topic that will be pursued by a new DFG Research Unit, which will examine the roles of “Macromolecular Complexes in the Localization of RNA”. Spokesperson for the new Unit is Professor Dierk Niessing of LMU’s Biomedical Center. The new interdisciplinary research network has received a DFG grant amounting to 2 million euros in its first funding period.
Complex supply chains
The intracellular transport of cargoes including mRNAs is carried out by a dedicated set of molecular transportation systems, which are made up of motor proteins and a large set of accessory factors that are assembled into a number of large multiprotein complexes. The motor proteins interact with so-called microtubules and/or microfilaments that form part of the so-called cytoskeleton, which serves both as a structural support and a routing network within the cell. Microtubules and microfilaments are themselves made up of repeated subunits, along which motor proteins, powered by metabolic energy, proceed stepwise, thus conveying their attached cargoes to their designated destinations. In some cell types, certain cargoes must be transported for relatively long distances. Neurons, for instance, typically possess a single lengthy process, called the axon, which extends from the so-called cell body (where the nucleus is located) to the synapse. The synapse is in turn responsible for the transmission of nerve impulses to the next neuron in the network – a highly specialized process which is crucially dependent on the synthesis of the required proteins “on site”.
“Transport of mRNAs is regulated by a dedicated set of components, but very little is known about how these factors interact to control this essential process,” says Niessing. He and his colleagues in the new Research Unit intend to characterize – for the first time – all of the components of the relevant transport complexes, and will elucidate their structure and function in several model organisms, including Saccharomyces cerevisiae (brewer’s yeast), a filamentous fungus, the fruitfly Drosophila melanogaster and the mouse. “The new Research Unit provides the ideal context for this systematic approach, as it brings together specialists in diverse disciplines such as cell biology, structural biology and bioinformatics,” Niessing points out.
Three LMU projects
Researchers based at LMU will tackle three of the Research Unit‘s subprojects: In a long-term collaboration with Ralf Jansen (Tübingen University), Co-Spokesperson for the venture, Niessing has previously demonstrated in yeast how, with the help of specific adaptor proteins, a particular subtype of the motor protein myosin is assembled into an active transport complex containing mRNA-binding proteins. Niessing and his team now intend to study the function of this complex in greater detail. The other two projects involving LMU biologists will investigate mRNA transport specifically in nerve cells, and will be led by Dierk Niessing and Professor Michael Kiebler, Director of the Institute for Cell Biology at the Biomedical Center.
DFG Research Units enable researchers to explore innovative approaches to the solution of current problems in their respective fields of interest. The new Research Unit hosted by LMU also includes groups based at the universities of Tübingen, Frankfurt and Düsseldorf, at the Max Planck Institute for Developmental Biology in Tübingen and the European Molecular Biology Laboratory (EMBL) in Heidelberg.