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Role of Ribonucleoprotein Complexes in Neurodevelopment and in the Physiopathology of Neurological Diseases

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Ribonucleoprotein particles containing RNAs and proteins are essential complexes in all living cells. Several of them constitute general stable machineries responsible for gene expression, as, for instance, spliceosomes and ribosomes whereas others like the RNA-induced silencing complex (RISC) rather regulate ...

Ribonucleoprotein particles containing RNAs and proteins are essential complexes in all living cells. Several of them constitute general stable machineries responsible for gene expression, as, for instance, spliceosomes and ribosomes whereas others like the RNA-induced silencing complex (RISC) rather regulate the gene expression processes. Messenger ribonucleoproteic particules (mRNPs) are complexes containing proteins that directly or indirectly interact with mRNAs. They are involved in most steps of mRNA synthesis, transport, activity and degradation, which contribute to development and cell functions. Regulation of mRNP metabolism is particularly important for highly specialized cells like neurons. Indeed, during development, trafficking of mRNAs and local translation to both axonal and dendritic growth cones play a crucial role in extensions elongation and pathfinding to regulate neuronal growth. After synapse formation, mRNAs continue to be transported to dendrites and axons and to be locally translated at the synapse thus participating to synaptic function and maintenance in adults. This process is at the molecular basis of synaptic plasticity and underlies the learning and memory processes.

The mRNA transport along dendrites and axons is performed by the RNA granules, a particular class of mRNPs that contain ribosomes associated with translationally repressed mRNAs. These granules are transported along the dendrites and axons, by ‘sliding’ on microtubules until synapses, providing local mRNA translation upon specific stimuli. Impairment of such spatio-temporal regulation could alter the ability to respond to injury or local stimuli within axons and dendrites. Consistent with this view, disruption of mRNA localization and/or localized mRNA translation may contribute to pathophysiology of neuronal diseases such as Fragile X syndrome (FXS) and Spinal Muscular Atrophy (SMA). The two disorders are due to the functional absence of the Fragile X Mental Retardation Protein (FMRP) and the Survival of Motor Neuron (SMN), respectively. We can also mention RBFOX1, SRRM4 and MECP2 as factors involved in RNA metabolism and associated with neurological diseases. Furthermore, concerning neurodegeneration, we can underline TAR DNA-binding protein 43 (TDP-43) associated with frontotemporal lobar degeneration (FTLD-U) and amyotrophic lateral sclerosis (ALS).

With this Topic we aim to contribute to a better understanding of the links existing between the metabolism of RNA (mediated by various RNPs) and the pathophysiology of neurological disorders. For this reason, we incite the submission of reviews and original research papers focused on the following aspects of proteins components of RNPs and involved in neurological disorders:
- Functional characterization of RNA-binding involved in neurological disorders;
- RNP biogenesis and their role in various steps of mRNA metabolism from transcription to translation;
- Network of RNA & protein partners;
- Cellular models;
- Next-generation techniques to study the RNA metabolism, with particular attention to single molecules applications
- Non–coding RNA as biomarkers of neurological disorders

Last, but not least, the submission of studies representing in vitro or in cellulo proof of concept of RNA-based therapies of neurological disorders is also encouraged.


Keywords: Neurological Disorders, RNA Metabolism, RNA-binding, Biomarkers, Ribonucleuprotein


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