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

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.

Keywords: RNA granules; RNA-binding proteins; dendritic mRNA; local translation.

Figure 1

Identification of mRNAs localized to the dendrite-enriched stratum radiatum (SR) layer in hippocampal CA1. Three different groups comprehensively identified mRNAs localized in the hippocampal SR layer using next-generation RNA sequencing. In the hippocampus, somas align in the stratum pyramidale (SP) and dendrites elongate into the SR. Cajigas et al., Nakayama et al., and Ainsley et al. identified mRNAs localized to the hippocampal SP and SR layers after isolating the layers from rodents. Cajigas et al. identified mRNAs abundant in the SR of the rat hippocampal CA1 region. Nakayama et al. identified mRNAs that are more enriched in the SR layer compared with the SP layer in the mouse hippocampus. They also identified mRNAs that were localized to the SR but were reduced in the SR of RNA granule protein 105 (RNG105, also known as Caprin1) conditional knockout (cKO) mice that showed long-term memory impairment. Ainsley et al. identified ribosome-bound mRNAs in the hippocampal SR of fear-conditioned mice. In this review, we compared the SR-enriched mRNA lists from these studies (colored in brown) and focused on dendritic mRNAs identified in common in all of these studies (Supplementary Table S1).

Figure 2

Gene ontology (GO) categories in which the identified dendritic mRNAs were enriched. The three studies (Cajigas et al., 2012; Ainsley et al., 2014; Nakayama et al., 2017) were compared, and 78 mRNAs were found to be commonly identified in the studies (a). The 78 mRNAs were classified by GO enrichment analysis using DAVID 6.8. GO categories in which the mRNAs were significantly enriched (b), and the list of mRNAs included in the GO categories (c) are shown.