Vesicle-coupled mRNA transport and translation govern intracellular organelle networking.

Eukaryotic cells are highly compartmentalized, enabling sophisticated division of labour. For example, genetic information is stored in the nucleus while energy is produced in mitochondria. Despite this clear specialisation, compartments depend on intensive communication, including the exchange of metabolites and macromolecules. This is achieved through intracellular trafficking with membranous carriers such as endosomes, which constitute versatile transport vehicles. Key cargos include mRNAs and ribosomes that hitchhike on endosomes, linking RNA and membrane biology. In this review, we summarize recent advances showing how mRNAs are mechanistically attached to membranes of endosomes and lysosomal vesicles and how cargos are identified for transport. The encoded proteins illuminate the biological processes that rely on such spatiotemporal control. This is particularly true for the regulation of subcellular mitochondrial homeostasis, disclosing intensive multi-organelle networking. As a general concept, the underlying protein/protein and protein/RNA interactions exhibit significant redundancy yet are organized in a strict hierarchy with distinct core and accessory functions. This ensures both the robustness and specificity of mRNA hitchhiking.