Abstract
Activity-dependent regulation of gene expression is critical in experience-mediated changes in the brain. Although less appreciated than transcriptional control, translational control is a crucial regulatory step of activity-mediated gene expression in physiological and pathological conditions. In the first part of this review, we overview evidence demonstrating the importance of translational controls under the context of synaptic plasticity as well as learning and memory. Then, molecular mechanisms underlying the translational control, including post-translational modifications of translation factors, mTOR signaling pathway, and local translation, are explored. We also summarize how activity-dependent translational regulation is associated with neurodevelopmental and psychiatric disorders, such as autism spectrum disorder and depression. In the second part, we highlight how recent application of high-throughput sequencing techniques has added insight into genome-wide studies on translational regulation of neuronal genes. Sequencing-based strategies to identify molecular signatures of the active neuronal population responding to a specific stimulus are discussed. Overall, this review aims to highlight the implication of translational control for neuronal gene regulation and functions of the brain and to suggest prospects provided by the leading-edge techniques to study yet-unappreciated translational regulation in the nervous system.
Highlights
Translation is an essential process of gene expression where ribosomes synthesize polypeptide chains that will be folded into functional proteins by the guidance of mRNA templates
The mechanism underlying the selective inhibition of translation on particular mRNAs in Diamond-Blackfan Anemia (DBA) patients remains to be elucidated, the tissueand transcript-selective phenotype of the ribosomopathy supports the significance of tight controls of translational processes
Fragile X Syndrome (FXS) is caused by a loss of an RNA binding protein Fragile X Mental Retardation Protein (FMRP) that is associated with actively translating poly-ribosomes [14]
Summary
Neuron utilizes the changes in membrane potential to compute incoming signal and to transmit information. Long-term synaptic plasticity induced by a specific form of neural activation provided evidence that a neuronal electric signal that can induce persistent change lasting for a few days requires protein synthesis as shown in classic studies in Aplysia [18]. Transcriptional control and translational control together comprises critical steps in the regulation of protein level, multiple reports indicating low correlation of transcriptome and proteome [25,26,27] suggest that translational control may function as an independent module in activity-dependent gene expression control and that neuronal translational control deserves attention at least as much as transcriptional control of the nervous system
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