Structure and functions of RNA binding proteins. RNA binding proteins have dual sites of action. In the nucleus, many RNA binding proteins, such as TDP-43, SMN (SMN1 and 2), TIA-1 and FUS regulate mRNA splicing. RNA binding proteins are also present in the cytoplasm and neuronal arbors, where they regulate RNA transport, activity dependent protein synthesis and sequestration of unnecessary transcripts in response to stress. Each of the RNA binding proteins shown in the figure associate with stress granules. TIA-1, SMN and Pumillio-2 are important for trafficking of mRNA in axons and dendrites, which is mediated by microtubules (blue and mustard striped line) and molecular motors. At the synapse, different RNA binding proteins regulate activity dependent translation. Phosphorylation causes 4E-BP to dissociate from eIF4E, which initiates translation. FMRP inhibits this process; loss of FMRP expression (such as occurs in fragile X syndrome) leads to excessive synaptic protein synthesis and excessive dendritic spine density. In contrast, CPEB stimulates activity dependent translation in a process that might involve regulated protein aggregation . Activity dependent protein synthesis is modulated by microRNA. For instance, miR125 regulates the synthesis of mGluR and PSD-95 . miRNA are generated by action of the RISC complex and argonaute, which cleave precursors to generate the miRs. Adapted from Liu-Yesucevitz, et al. .