Gómez-Montalvo Jesús, Koutsogiannis Zisis, Maciver Sutherland K, de Obeso Fernández Del Valle Alvaro
Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Ave. Eugenio Garza Sada 2501, 64849, Monterrey, N.L, Mexico.
Centre for Discovery Brain Sciences, Edinburgh Medical School, Biomedical Sciences, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, Scotland, UK.
Microb Cell. 2025 Aug 26;12:231-241. doi: 10.15698/mic2025.08.858. eCollection 2025.
Programmed cell death (PCD) in unicellular organisms is not well characterized. This study investigated the transcriptomic response of 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 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 facultative human pathogen.
单细胞生物中的程序性细胞死亡（PCD）尚未得到充分表征。本研究调查了[具体生物名称未给出]对G418诱导的PCD的转录组反应，重点关注可变剪接（AS）的作用。RNA测序揭示了广泛的转录变化，在六小时的处理过程中影响了约70%的注释基因。该分析还突出了与细胞周期、蛋白水解和RNA剪接相关途径的显著改变。对AS事件的分析鉴定出18,748个差异剪接事件，主要是内含子保留（IR）。有趣的是，在未处理的细胞中，保留的内含子呈现出3'偏向性，而在PCD过程中这种模式转变为在整个基因体内均匀分布。此外，我们对滋养体阶段和变形虫PCD过程中的保留内含子进行了表征。相关性分析揭示了IR与转录水平之间存在显著的负相关，表明转录调控和转录后调控之间存在复杂的相互作用。IR的优势，以及其在PCD过程中的动态位置变化，指向了[具体生物名称未给出]PCD中的一种新型调控机制。这些发现为该生物体中PCD的分子机制提供了见解，有可能识别出新的治疗靶点，并使我们更好地理解这种在兼性人类病原体[具体生物名称未给出]中的过程。
