Making and breaking synapses through local mRNA regulation

Neurons are exquisitely polarized cells that extend intricate axonal and dendritic arbors. Developmental cues guide axons and dendrites into circuits by inducing rapid changes in local protein expression and cytoskeletal structure. Neurons can transduce these signals through local mRNA regulation. Here, we review the latest insights regarding post-transcriptional control of gene expression through mRNA transport and local protein synthesis in developing neurons. We focus on local mRNA regulation during axon growth and guidance, dendrite morphogenesis, and synapse formation and refinement. Dysregulated mRNA transport and translation in neurological disorders are also discussed. The collection of molecules and mechanisms reviewed includes sequence-specific RNA binding proteins, microtubule motors and adaptors, microRNAs, translation initiation factors, and the receptor-mediated signaling that modulates these molecules.

► Axonal mRNA profiling studies have identified that mRNA localization is developmentally regulated. ► Locally synthesized proteins can regulate gene expression and neuronal survival. ► Combinatorial regulation of specific mRNAs controls local translation and dendrite morphogenesis. ► RNA binding proteins have specific presynaptic and postsynaptic functions in neural circuit development. ► Local protein synthesis is required for the maintenance of developing synapses.