Comprehensive Genome-Wide Approaches to Activity-Dependent Translational Control in Neurons

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.

Building a (w)rapport between neurons and oligodendroglia: Reciprocal interactions underlying adaptive myelination

“…Neuronal activity has been shown to induce numerous changes in neurons, including broad transcriptional and translational changes (Choe and Cho, 2020;Flavell and Greenberg, 2008;Yap and Greenberg, 2018), providing many other candidates to induce adaptive myelination. For example, as with synaptic transmission, transmembrane proteins could induce effects with high spatial specificity, particularly if their expression is restricted to the structure that is to be myelinated (or not myelinated).…”

Homeostatic Roles of the Proteostasis Network in Dendrites

“…Though ribosomopathies have consequences throughout the body, some ribosomal subunit mutations are connected specifically to neurological disorders, such as those linked to cases of Autism Spectrum Disorder (ASD) and intellectual disability (ID) (Hetman and Slomnicki, 2019;Choe and Cho, 2020). Defects in ribosome function have also been connected to neurodegenerative diseases such as Alzheimer's disease (AD) (Ding et al, 2005;Hernández-Ortega et al, 2016) and Parkinson's disease (PD) (Taymans et al, 2015), and ribosomal frameshifting is implicated in repeat expansion disorders such as Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS) (Gao et al, 2017).…”

Regulatory effect of long-stranded non-coding RNA-CRNDE on neurodegeneration during retinal ischemia-reperfusion

“…Recent studies have shown that aberrant lncRNA expression is implicated in multiple human diseases ranging from neurodegenerative diseases to cancers. Furthermore, the homeostasis and plasticity of neuronal signaling are required for sophisticated gene regulatory mechanisms [ 10 ]. Given the important roles of lncRNAs in gene regulation and tissue homeostasis, the findings suggest that lncRNAs play critical roles in neurodegeneration in RIR injury.…”