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ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Neuroplasticity and Development
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1392408
This article is part of the Research Topic Come as You R(NA): Post-transcriptional Regulation Will Do the Rest View all 10 articles

A comparison of basal and activity-dependent exon splicing in cortical-patterned neurons of human and mouse origin

Provisionally accepted
Owen Dando Owen Dando 1*Jamie McQueen Jamie McQueen 1Karen Burr Karen Burr 1Peter C. Kind Peter C. Kind 1Siddharthan Chandran Siddharthan Chandran 1Giles E. Hardingham Giles E. Hardingham 2*Jing Qiu Jing Qiu 1*
  • 1 University of Edinburgh, Edinburgh, Scotland, United Kingdom
  • 2 UK Dementia Research Centre, University of Edinburgh, Edinburgh, United Kingdom

The final, formatted version of the article will be published soon.

    Rodent studies have shown that alternative splicing in neurons plays important roles in development and maturity, and is regulatable by signals such as electrical activity. However, rodenthuman similarities are less well explored. We compared basal and activity-dependent exon splicing in cortical-patterned human ESC-derived neurons with that in cortical mouse ESC-derived neurons, primary mouse cortical neurons at two developmental stages, and mouse hippocampal neurons, focussing on conserved orthologous exons. Both basal exon inclusion levels and activity-dependent changes in splicing showed human-mouse correlation. Conserved activity regulated exons are enriched in RBFOX, SAM68, NOVA and PTBP targets, and centred on cytoskeletal organisation, mRNA processing, and synaptic signaling genes. However, human-mouse correlations were weaker than inter-mouse comparisons of neurons from different brain regions, developmental stages and origin (ESC vs. primary), suggestive of some inter-species divergence. The set of genes where activity-dependent splicing was observed only in human neurons were dominated by those involved in lipid biosynthesis, signaling and trafficking. Study of human exon splicing in mouse Tc1 neurons carrying human chromosome-21 showed that neuronal basal exon inclusion was influenced by cisacting sequences, although may not be sufficient to confer activity-responsiveness in an allospecific environment. Overall, these comparisons suggest that neuronal alternative splicing should be confirmed in a human-relevant system even when exon structure is evolutionarily conserved.

    Keywords: RNA-Seq - RNA sequencing, Gene Expression, Neuronal activity, Calcium Signaling, evolutionary conservation and divergence, Alternative Splicing

    Received: 27 Feb 2024; Accepted: 05 Aug 2024.

    Copyright: © 2024 Dando, McQueen, Burr, Kind, Chandran, Hardingham and Qiu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Owen Dando, University of Edinburgh, Edinburgh, EH8 9YL, Scotland, United Kingdom
    Giles E. Hardingham, UK Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9XD, United Kingdom
    Jing Qiu, University of Edinburgh, Edinburgh, EH8 9YL, Scotland, United Kingdom

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