09/09/24
In neurons, a diverse array of coding and non-coding RNAs localise to axons, dendrites, and synapses, facilitating rapid responses to local needs, such as axon and dendrite extension and branching, synapse formation, and synaptic plasticity. However, relatively little is known about the regulatory mechanisms different RNA types undergo in different parts of the neuronal periphery, and their variety of fates and functions, ensuring normal development and function of the compartments in which the molecules reside.
CDN researcher Richard Taylor and alumnus Nikolas Nikolaou (University of Bath) discuss our current understanding of RNA subclass diversity in neuronal subcellular compartments in their review in Frontiers in Molecular Neuroscience .
Taylor and Nikolaou highlight the diverse types of RNA that localise to axons, dendrites, and synapses, as well as exosomes that enable the transfer of RNAs to neighbouring cells when secreted. They offer a synthesised summary of the key datasets characterising the types or classes found within each subcellular compartment across different sample types, and compare the transcriptomes for the different compartments.
The authors go on to provide an overview of the known fates and functions of the different RNA classes discussed, as well as the implications for the development and maintenance of each subcellular compartment. Recent studies suggest that misregulation of local RNA regulation may be a driver of synapse loss preceding neuronal death in neurodegenerative diseases.
The review also focuses on recent advances in third-generation sequencing technologies that hold the power to revolutionise our understanding of splice isoform diversity and RNA modifications in local transcriptomes. These technologies will allow alternative isoforms that are specific to axons, dendrites and synapses to be identified at a finer resolution than previously possible. Single-cell-based long-read sequencing will further give insights into cell-specific isoform diversity at subcellular resolution. These new capabilities will likely transform our understanding of how individual genes can regulate both their own expression and that of other genes, and assert regulatory influence on local transcriptomes and proteomes.
