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A stochastic RNA editing process targets a select number of sites in individual Drosophila glutamatergic motoneurons

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Crane, Andrés B, Inouye, Michiko O, Jetti, Suresh K, Littleton, J Troy·2025·eLife
DOI 10.7554/elife.108282.2PMC PMC11118563

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Abstract

RNA editing is a post-transcriptional source of protein diversity and occurs across the animal kingdom. Given the complete profile of mRNA targets and their editing rate in individual cells is unclear, single-cell RNA transcriptomes obtained by Patch-seq from Drosophila larval glutamatergic motoneuron subtypes were analyzed to determine the most highly edited targets and identify single neuron editing rules. 316 high-confidence A-to-I canonical RNA edit sites were identified, with 60 causing missense amino acid changes predicted to alter proteins regulating membrane excitability, synaptic transmission, or neuronal function. Twenty-seven canonical sites were edited at >90% frequency as observed for editing of mammalian AMPA receptors. However, most sites were edited at lower levels and generated variable expression of edited and unedited mRNAs, suggesting stochastic editing that may provide a mechanism to fine-tune synaptic function similar to alternative splicing. Noncanonical editing was also found to occur in these neurons, including a C-to-U edit that altered an amino acid in the capsid hinge domain of the synaptic plasticity regulator Arc1. Together, these data provide insights into how the RNA editing landscape may alter protein function to modulate the properties of two well-characterized neuronal populations in Drosophila .

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Metadata

Authors
Crane, A. B., Inouye, M. O., Jetti, S. K., & Littleton, J. T.
Affiliations
Massachusetts Institute of Technology (US)
Corresponding author
Littleton, J Troy
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2025-11-20
Volume
14
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.108282.2
PMC
PMC11118563
OpenAlex
W4397045793
Cited by
0
References
2
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by-nc-nd)
Funders
  • National Institute of Neurological Disorders and Stroke (NS117588, F31NS118948)
  • National Institute of Mental Health (MH104536)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
RNA editing, A-to-I RNA editing, glutamatergic neurons, single-cell transcriptomics, editing sites, AMPA receptors, acetylcholine receptor, shank, synaptic vesicle fusion, endocytosis, ARC1, larval development

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