RNA transport and local translation in neurodevelopmental and neurodegenerative disease (original) (raw)

“…Conversely, understanding which mRNAs and/or miRNAs are regulated by these mechanisms will be a crucial step to more broadly appreciating the roles of membranous transport in controlling activity-dependent translation in neurons. Lastly, given that defects in RNA trafficking and translation are tightly linked to genetic disorders such as ALS and Fragile X syndrome (Wang et al, 2016b;Fernandopulle et al, 2021), further investigation into the role of organelle/local translation cross-talk in synaptic dysfunction will surely add to this body of knowledge. As research in this area is only in its infancy, it is likely that further investigation will reveal fundamental roles for endosomes, lysosomes, and mitochondria in activitydependent local translation and how they are disrupted in neurological disease.…”

Section: Discussionmentioning

“…RNAs are trafficked from their site of production in the nucleus to distal compartments via long-range transport mechanisms along dendrites and axons (see Fernandopulle et al, 2021, for a recent review). For transport, RNAs and RBPs self-assemble into macromolecular ribonucleoprotein (RNP) complexes, termed RNP granules (Formicola et al, 2019).…”

Section: Transport Of Mrna To Remote Neuronal Compartmentsmentioning

“…A more complete understanding of how mRNAs map across neurons needs to be complemented with information on mRNA transport and release dynamics under baseline conditions and following changes in activity that promote plasticity. The 3′ and 5′untranslated regions (UTRs) contain elements important for the binding, transport, localization, and regulated translation of mRNAs [17]. Pointing to the importance of translational regulation in neurons, the 3′ UTRs of neuronal mRNAs, particularly those localized to axons and dendrites, are significantly longer than those of other cell types [18].…”

Section: What Roles Do Mrna Transport and Local Translation Play In Synaptic Proteostasis?mentioning

“…In response to specific cues or demands, mRNAs undergo coordinated local translation. RBPs are key players in this process, which function by recognizing and binding to one or more sequences on their target mRNAs, forming ribonucleoprotein (RNP) complexes ( Glisovic et al, 2008 ; Czaplinski, 2014 ; Fernandopulle et al, 2021 ). This complex regulates multiple post-transcriptional functions, including splicing, mRNA localization, and translation.…”

Section: Introductionmentioning