Working Paper Review Version 1 This version is not peer-reviewed

mRNA Trafficking in the Nervous System – A Key Mechanism of the Involvement of Activity Regulated Cytoskeleton Associated Protein (Arc) in Synaptic Plasticity

Version 1 : Received: 7 July 2021 / Approved: 8 July 2021 / Online: 8 July 2021 (10:04:52 CEST)

How to cite: Fila, M.; Diaz, L.; Szczepanska, J.; Pawlowska, E.; Blasiak, J. mRNA Trafficking in the Nervous System – A Key Mechanism of the Involvement of Activity Regulated Cytoskeleton Associated Protein (Arc) in Synaptic Plasticity. Preprints 2021, 2021070187 Fila, M.; Diaz, L.; Szczepanska, J.; Pawlowska, E.; Blasiak, J. mRNA Trafficking in the Nervous System – A Key Mechanism of the Involvement of Activity Regulated Cytoskeleton Associated Protein (Arc) in Synaptic Plasticity. Preprints 2021, 2021070187

Abstract

Synaptic activity mediates information storage and memory consolidation in the brain and requires a fast de novo synthesis of mRNAs in the nucleus and proteins in synapses. Intracellular localization of a protein can be achieved by mRNA trafficking and localized translation. Activity regulated cytoskeleton associated protein (Arc) is a master regulator of synaptic plasticity and plays an important role in the controlling of large signaling networks linked with learning, memory consolidation and behavior. Transcription of the Arc gene may be induced by a short behavioral event resulting in synaptic activation. Arc mRNA is exported into cytoplasm and can be trafficked into dendrite of an activated synapse where it is docked and translated. Structure of Arc is similar to the viral GAG (group-specific antigen) protein and phylogenic analysis suggests that Arc may originate from the family of Ty3/Gypsy retrotransposons. Therefore, Arc might evolve through “domestication” of retroviruses. Arc can form a capsid-like structure that encapsulates a retrovirus-like sentence in 3’-UTR (untranslated region) of Arc mRNA. This complex can be loaded into extracellular vesicles and transported to other neurons or muscle cells carrying not only genetic information but also regulatory signals within neuronal network. Therefore, Arc mRNA inter- and intramolecular trafficking are essential for the modulation of synaptic activity required for memory consolidation and cognitive functions.

Subject Areas

mRNA trafficking; synaptic plasticity; activity regulated cytoskeleton associated protein; Arc; intercellular transfer of genetic information; retroviral sequences in the human genome

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