Abstract
Small non-coding RNAs are essential for transcription, translation and gene regulation in all cell types, but are particularly important in neurons, with known roles in neurodevelopment, neuroplasticity and neurological disease. Many small non-coding RNAs are directly involved in the post-transcriptional modification of other RNA species, while others are themselves substrates for modification, or are functionally modulated by modification of their target RNAs. In this review, we explore the known and potential functions of several distinct classes of small non-coding RNAs in the mammalian brain, focusing on the newly recognised interplay between the epitranscriptome and the activity of small RNAs. We discuss the potential for this relationship to influence the spatial and temporal dynamics of gene activation in the brain, and predict that further research in the field of epitranscriptomics will identify interactions between small RNAs and RNA modifications which are essential for higher order brain functions such as learning and memory.
Highlights
Cells produce vast amounts of RNA which lack protein-coding potential, including many functional RNA molecules less than 200 nucleotides in size
Regulation of gene expression is emerging as a surprising mechanism of action for small RNAs with functions that were believed to be entirely unrelated; for example, transfer RNA fragments have been implicated in stress responses and in transgenerational epigenetic inheritance [5], while small nuclear RNAs can influence alternative splicing [6]
We explore several classes of small non-coding RNAs which are known to be expressed in the mammalian brain, discuss their roles in brain function, and consider how post-transcriptional modifications of small RNAs and their targets can increase the information-carrying capacity of neuronal RNA
Summary
Cells produce vast amounts of RNA which lack protein-coding potential, including many functional RNA molecules less than 200 nucleotides in size These small non-coding RNAs arise through a multitude of distinct biogenesis pathways, and are involved in cellular processes including transcription, splicing, translation, RNA modification, and regulation of gene expression through several mechanisms (Table 1). We predict that as new technology permits the profiling and functional interrogation of the epitranscriptome with improved temporal and spatial resolution, new mechanisms of gene regulation and cellular signalling will be identified at the interface of small RNA biology and RNA modification and shown to be essential for higher-order neurological function, including learning and memory
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