Cytoplasmic RNA-binding proteins and the control of complex brain function

The formation and maintenance of neural circuits in the mammal central nervous system (CNS) require the coordinated expression of genes not just at the transcriptional level, but at the translational level as well. Recent evidence shows that regulated messenger RNA (mRNA) translation is necessary for certain forms of synaptic plasticity, the cellular basis of learning and memory. In addition, regulated translation helps guide axonal growth cones to their targets on other neurons or at the neuromuscular junction. Several neurologic syndromes have been correlated with and indeed may be caused by aberrant translation; one important example is the fragile X mental retardation syndrome. Although translation in the CNS is regulated by multiple mechanisms and factors, we focus this review on regulatory mRNA-binding proteins with particular emphasis on fragile X mental retardation protein (FMRP) and cytoplasmic polyadenylation element binding (CPEB) because they have been shown to be at the nexus of translational control and brain function in health and disease.