Alternative splicing drives a dynamic transcriptomic response during Acanthamoeba castellanii programmed cell death
Authors:Jesús Gómez-Montalvo1, Zisis Koutsogiannis2, Sutherland K. Maciver2 and Alvaro de Obeso Fernández del Valle1
1 Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Ave. Eugenio Garza Sada 2501, 64849, Monterrey, N.L, Mexico. 2 Centre for Discovery Brain Sciences, Edinburgh Medical School, Biomedical Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, Scovtland, UK.
Keywords:
Acanthamoeba castellanii, programmed cell death, alternative splicing, intron retention, transcriptomics.
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Conflict of interest statement:
The authors declare no competing interest.
Please cite this article as:
Jesús Gómez-Montalvo, Zisis Koutsogiannis, Sutherland K. Maciver and Alvaro de Obeso Fernández del Valle (2025). Alternative splicing drives a dynamic transcriptomic response during Acanthamoeba castellanii programmed cell death. Microbial Cell 12: 231-241. doi: 10.15698/mic2025.08.858
© 2025 Gómez-Montalvo et al. This is an open-access article released under the terms of the Creative Commons Attrib-ution (CC BY) license, which allows the unrestricted use, distribu-tion, and reproduction in any medium, provided the original au-thor and source are acknowledged.
Abstract:
Programmed cell death (PCD) in unicellular organisms is not well characterized. This study investigated the transcriptomic response of Acanthamoeba castellanii to G418-induced PCD, focusing on the role of alternative splicing (AS). RNA sequencing revealed extensive transcriptional changes, affecting approximately 70% of annotated genes over six hours of treatment. This analysis also highlighted significant alterations in pathways related to cell cycle, proteolysis, and RNA splicing. Analysis of AS events identified 18,748 differentially spliced events, predominantly intron retention (IR). Interestingly, retained introns displayed a 3′ bias in untreated cells, a pattern that shifted towards uniform distribution throughout the gene body during PCD. Additionally, we characterized retained introns during trophozoite stage and during PCD of the amoeba. Correlational analysis revealed a significant negative correlation between IR and transcript levels, suggesting a complex interplay between transcriptional and post-transcriptional regulation. The predominance of IR, coupled with its dynamic positional shift during PCD, points to a novel regulatory mechanism in A. castellanii PCD. These findings provide insights into the molecular mechanisms underlying PCD in this organism, potentially identifying new therapeutic targets and allowing us a better understanding of such process in A. castellanii, a facultative human pathogen.
doi: 10.15698/mic2025.08.858
Volume 12, pp. 231 to 241, published 26/08/2025.