Proteostasis and RNA Binding Proteins in Synaptic Plasticity and in the Pathogenesis of Neuropsychiatric Disorders

Figure 1

The trials and tribulations of RBPs and RNPs. (a) RBPs assemble cotranscriptionally and regulate mRNA splicing and modification preventing the coassembly of multiple mRNAs per RNP. Motifs in the 5′UTR and 3′UTR as well as retained intronic sequences facilitate dendritic targeting of RNPs. (b) RBPs transport mRNAs along microtubules to destinations dictated by the cargo mRNA sequence. Through input-specific events, synapses or dendritic branches may autonomously regulate their mRNA content. (c) Excitatory synapses at dendritic spines greatly outnumber mRNAs in dendrites and even more so counting inhibitory synapses. Despite being sparsely distributed, local mRNAs contribute significantly to synaptic function. (d) Upon synaptic stimulation, RBP function determines mRNA fate. Derepression by translational repressors can be followed by promotion of translation by RBPs like Sam68 (purple). Translation is counterbalanced by proteasomal or lysosomal degradation.