Cataloguing and Selection of mRNAs Localized to Dendrites in Neurons and Regulated by RNA-Binding Proteins in RNA Granules.

Ohashi Ohashi,Shiina Shiina

doi:10.3390/biom10020167

Abstract

Spatiotemporal translational regulation plays a key role in determining cell fate and function. Specifically, in neurons, local translation in dendrites is essential for synaptic plasticity and long-term memory formation. To achieve local translation, RNA-binding proteins in RNA granules regulate target mRNA stability, localization, and translation. To date, mRNAs localized to dendrites have been identified by comprehensive analyses. In addition, mRNAs associated with and regulated by RNA-binding proteins have been identified using various methods in many studies. However, the results obtained from these numerous studies have not been compiled together. In this review, we have catalogued mRNAs that are localized to dendrites and are associated with and regulated by the RNA-binding proteins fragile X mental retardation protein (FMRP), RNA granule protein 105 (RNG105, also known as Caprin1), Ras-GAP SH3 domain binding protein (G3BP), cytoplasmic polyadenylation element binding protein 1 (CPEB1), and staufen double-stranded RNA binding proteins 1 and 2 (Stau1 and Stau2) in RNA granules. This review provides comprehensive information on dendritic mRNAs, the neuronal functions of mRNA-encoded proteins, the association of dendritic mRNAs with RNA-binding proteins in RNA granules, and the effects of RNA-binding proteins on mRNA regulation. These findings provide insights into the mechanistic basis of protein-synthesis-dependent synaptic plasticity and memory formation and contribute to future efforts to understand the physiological implications of local regulation of dendritic mRNAs in neurons.

Highlights

Spatiotemporal translational regulation is key to increasing the concentration of specific proteins to exert their functions at specific timings and locations in cells
Local translation in axons is mainly required for axon outgrowth and maintenance, and local translation in dendrites is necessary for synaptic plasticity and long-term memory formation [1–4]
In 1996, Kang and Schuman revealed that long-term potentiation (LTP) occurs in the stratum radiatum (SR), which is a dendrite-enriched region in hippocampal CA1, even after the SR was isolated from the cell-soma-enriched stratum pyramidale (SP)

Summary

Introduction

Spatiotemporal translational regulation is key to increasing the concentration of specific proteins to exert their functions at specific timings and locations in cells. As the neuropil layer from the hippocampal CA1 region of adult rat brains and subjected them to These three studies used different strategies to identify dendritic mRNAs in term of abundance, relative enrichment, and ribosome binding. Farris et al identified mRNAs localized in the hippocampal subregions (CA1, CA2, CA3, and the dentate gyrus) of the adult mouse hippocampus [18] They found that 68 of the 78 mRNAs overlapped as mRNAs enriched in the SR layer of the CA1 region among their study and the three studies above [18], supporting the reliable dendritic localization of the commonly identified mRNAs. The general functions and neuronal/brain functions of these 78 mRNA-encoded proteins are summarized in Supplementary Table S1 [19–194]. These mRNAs were enriched mainly in the categories of “ribosome”, “synapse”, “elongation factor”, “dendritic spine”, and “ionotropic glutamate receptor complex” (Figure 2b,c)

Methods for Identifying RNA–Protein Interactions

Effects of the RNA-Binding Proteins on mRNA Regulation

Future Perspectives