Making sense of mRNA landscapes: Translation control in neurodevelopment. (17th June 2021)

• Record Type: Journal Article
• Authors: Park, Yongkyu; Page, Nicholas; Salamon, Iva; Li, Diana; Rasin, Mladen‐Roko
• Is Part Of: Wiley interdisciplinary reviews. Volume 13:Number 1(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-06-17
• Subjects: mRNA -- neurodevelopment -- translation; RNA -- Periodicals; 572.8805
• DOI: 10.1002/wrna.1674
• Languages: English
• ISSNs: 1757-7004

Abstract

Abstract: Like all other parts of the central nervous system, the mammalian neocortex undergoes temporally ordered set of developmental events, including proliferation, differentiation, migration, cellular identity, synaptogenesis, connectivity formation, and plasticity changes. These neurodevelopmental mechanisms have been characterized by studies focused on transcriptional control. Recent findings, however, have shown that the spatiotemporal regulation of post‐transcriptional steps like alternative splicing, mRNA traffic/localization, mRNA stability/decay, and finally repression/derepression of protein synthesis (mRNA translation) have become just as central to the neurodevelopment as transcriptional control. A number of dynamic players act post‐transcriptionally in the neocortex to regulate these steps, as RNA binding proteins (RBPs), ribosomal proteins (RPs), long non‐coding RNAs, and/or microRNA. Remarkably, mutations in these post‐transcriptional regulators have been associated with neurodevelopmental, neurodegenerative, inherited, or often co‐morbid disorders, such as microcephaly, autism, epilepsy, intellectual disability, white matter diseases, Rett‐syndrome like phenotype, spinocerebellar ataxia, and amyotrophic lateral sclerosis. Here, we focus on the current state, advanced methodologies and pitfalls of this exciting and upcoming field of RNA metabolism with vast potential in understanding fundamental neurodevelopmental processes and pathologies. This article is categorized under: Translation > Translation Regulation RNA in Disease and Development > RNA in Disease RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications Abstract : The spatiotemporal regulation of post‐transcriptional steps such as repression/derepression of protein synthesis (mRNA translation) is central to the neurodevelopment of neocortex. We focus on the current state of this exciting and upcoming mRNA translation field in understanding fundamental developmental processes and associated neuropsychiatric pathologies. (left) Role of RNA binding proteins (RBPs) are immersed into post‐transcriptional goal, to regulate the ultimate level of protein in developing cell. (right) mRNA translation regulated by RBPs (arrow) was associated with major developmental steps in developing cells of central nervous system, including (a, b) stem cells, (c) migrating, and (d) differentiating neurons.