Novel Molecular Basis for Synapse Formation: Small Non-coding Vault RNA Functions as a Riboregulator of MEK1 to Modulate Synaptogenesis.

Shuji Wakatsuki,Toshiyuki Araki

doi:10.3389/fnmol.2021.748721

Shuji Wakatsuki, Toshiyuki Araki

Open Access

https://doi.org/10.3389/fnmol.2021.748721

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Abstract

Small non-coding vault RNAs (vtRNAs) have been described as a component of the vault complex, a hollow-and-barrel-shaped ribonucleoprotein complex found in most eukaryotes. It has been suggested that the function of vtRNAs might not be limited to simply maintaining the structure of the vault complex. Despite the increasing research on vtRNAs, little is known about their physiological functions. Recently, we have shown that murine vtRNA (mvtRNA) up-regulates synaptogenesis by activating the mitogen activated protein kinase (MAPK) signaling pathway. mvtRNA binds to and activates mitogen activated protein kinase 1 (MEK1), and thereby enhances MEK1-mediated extracellular signal-regulated kinase activation. Here, we introduce the regulatory mechanism of MAPK signaling in synaptogenesis by vtRNAs and discuss the possibility as a novel molecular basis for synapse formation.

Highlights

Non-coding RNAs function at the RNA level without being translated into proteins
Knockdown of the mvp gene by RNA interference (RNAi) decreased AuroraA expression levels and local translational activity in neurites. These results suggest that the vault complex may function as a transporter for both mRNAs translated in dendrites and AuroraA, which are both involved in the regulation of local translation
In neurites with RNAimediated downregulation of mvp or antisense oligonucleotidemediated downregulation of mouse vtRNA (mvtRNA), we observed reduced extracellular signal-regulated kinase (ERK) activation, local translation and synaptic formation (Wakatsuki et al, 2021b). These results suggest that mvtRNA acts on ERK activity to potentiate local translation in neurites and positively regulate synaptogenesis (Figure 1)

Summary

INTRODUCTION

Non-coding RNAs (ncRNAs) function at the RNA level without being translated into proteins. Knockdown of the mvp gene by RNAi decreased AuroraA expression levels and local translational activity in neurites These results suggest that the vault complex may function as a transporter for both mRNAs translated in dendrites and AuroraA, which are both involved in the regulation of local translation. This may suggest the possibility that mvtRNA binding to MEK alters its molecular structure and enhances its activity (Figure 2B). We observed that mvtRNA regulates ERK activity but has little effect on AKT activity (Wakatsuki et al, 2021b) These results suggest that vtRNAs may be involved in specific subcellular signaling elicited by neurotransmitter receptors. It is necessary to clarify how the mvtRNA binding affects the molecular structure of MEK or alters the affinity of MEK to ERK to activate MAPK signaling

CONCLUSION AND FUTURE DIRECTIONS

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