Steady-state RNA levels are controlled by the balance between RNA synthesis and RNA turnover. A selective RNA turnover mechanism that has received recent attention in neurons is nonsense-mediated RNA decay (NMD). NMD has been shown to influence neural development, neural stem cell differentiation decisions, axon guidance and synaptic plasticity. In humans, NMD factor gene mutations cause some forms of intellectual disability and are associated with neurodevelopmental disorders, including schizophrenia and autism spectrum disorder. Impairments in NMD are linked to neurodegenerative disorders, including amyotrophic lateral sclerosis. We discuss these findings, their clinical implications and challenges for the future.
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This work was supported by US National Institute of Health grants NS056306 (S.J.) and R01 GM111838 (M.F.W.).
Nature Reviews Neuroscience thanks D. Silver and the other anonymous reviewers for their contribution to the peer review of this work.
The authors declare no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
- RNA turnover
Degradation of RNAs; typically achieved through the action of specific nucleases.
- RNA surveillance
The recognition and subsequent elimination of abnormal RNAs.
Mutant proteins that antagonize the function of the wild-type protein.
RNAs, including those coding for protein (mRNAs).
- Genome-wide studies
Analyses of the majority of the genes in a genome (for example, RNA sequencing analysis determines the level of RNAs transcribed from all significantly expressed genes in the genome).
Codons that are in the same frame as the initiator codon.
- Untranslated regions
(UTRs). The regions of an mRNA upstream and downstream of the coding region (that is, the 5′ UTR is upstream of the initiator codon and the 3′ UTR is downstream of the stop codon).
Loss of one copy of a gene from a diploid organism.
- Commissural axons
Neurites (projections from the cell body) that cross the midline of the CNS to the other side of the nervous system.
Insertions and deletions downstream of the initiator codon that are not a multiple of three and thus shift the reading frame (this leads to altered amino acids in the encoded protein downstream of the frameshift).
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Jaffrey, S.R., Wilkinson, M.F. Nonsense-mediated RNA decay in the brain: emerging modulator of neural development and disease. Nat Rev Neurosci 19, 715–728 (2018). https://doi.org/10.1038/s41583-018-0079-z
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