Why study mRNA localization?

Work of the last 20 years has uncovered the great importance of gene regulation at the posttranscriptional level for a plethora of different cellular functions. One particularly powerful RNA-mediated regulatory mechanism is the intracellular transport of translationally silenced transcripts by motor-protein containing complexes and their subsequent translational activation at subcellular sites. This essential mechanism is conserved from fungi, plants, and invertebrates to mammals. Messenger RNA (mRNA) localization critically contributes to diverse processes such as embryogenesis, stem-cell differentiation, neurogenesis, and synaptic function. Besides, the molecular motors that move along actin filaments or microtubules, such transport complexes consist of RNA-binding proteins for the specific recognition of localized transcripts, RNA helicases, adapter proteins, and splicing factors.

To date, budding yeast is the only model organism where all essential protein factors for actin-dependent mRNA localization have been identified. Recently, additional genetically amenable fungal model systems like Ustilago maydis have been established to study the microtubule-dependent mRNA transport machinery. In metazoa, the oogenesis and early embryogenesis of Drosophila provide particularly successful examples for elucidating the biological function and molecular mechanism of mRNA localization. Here, the determination of the body axes depends on the correct localization of maternally provided mRNAs in the oocyte and egg. In vertebrates, for instance neuronal cells require mRNA localization to their pre- and post-synaptic areas and subsequent translation for learning and memory.

Thanks to technological advances as well as recent successes in in vitro reconstitution experiments, we are now in the position to dissect the molecular pathways underlying the localization of translationally silenced mRNAs at an unprecedented level. To lever on these new developments, the FOR2333 Research Unit unites researchers with complementary expertise to foster collaborations and thus to cross-fertilize the research field with these new developments. This includes different model organisms and diverse technological backgrounds from genetics, and biochemistry, to structural biology and bioinformatics.

The FOR2333 Research Unit wishes to address three key issues:

How is specificity for localizing mRNAs achieved on a molecular level, especially in cases when multifunctional RNA-binding proteins participate?

Which proteins and RNA motifs contribute to translational repression during transport and by which mechanisms?

How are mRNAs tethered to endomembranes and what is the function of co-transport of mRNAs with membranes?