Department of Animal Health, NEIKER- Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Department of Applied Mathematics, NEIKER- Basque Institute for Agricultural Research and Development, Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, Spain.
Front Immunol. 2024 Mar 1;15:1354500. doi: 10.3389/fimmu.2024.1354500. eCollection 2024.
Little is known about the role of alternative splicing (AS) in regulating gene expression in -infected individuals in distinct stages of infection. Pre-mRNA AS consists of the removal of introns and the assembly of exons contained in eukaryotic genes. AS events can influence transcript stability or structure with important physiological consequences. Using RNA-Seq data from peripheral blood (PB) and ileocecal valve (ICV) samples collected from Holstein cattle with focal and diffuse paratuberculosis (PTB)-associated histopathological lesions in gut tissues and without lesions (controls), we detected differential AS profiles between the infected and control groups. Four of the identified AS events were experimentally validated by reverse transcription-digital droplet PCR (RT-ddPCR). AS events in several genes correlated with changes in gene expression. In the ICV of animals with diffuse lesions, for instance, alternatively spliced genes correlated with changes in the expression of genes involved in endocytosis, antigen processing and presentation, complement activation, and several inflammatory and autoimmune diseases in humans. Taken together, our results identified common mechanisms of AS involvement in the pathogenesis of PTB and human diseases and shed light on novel diagnostic and therapeutic interventions to control these diseases.
关于在感染的不同阶段感染 - 的个体中，可变剪接（AS）在调节基因表达中的作用知之甚少。前体 mRNA 的 AS 包括真核基因中内含子的去除和外显子的组装。AS 事件会影响转录本的稳定性或结构，从而产生重要的生理后果。我们使用来自患有局灶性和弥漫性副结核病（PTB）相关组织病理学病变（病变）和无病变（对照）的荷斯坦牛的外周血（PB）和回肠瓣（ICV）样本的 RNA-Seq 数据，检测了感染组和对照组之间的差异 AS 谱。通过逆转录 - 数字液滴 PCR（RT-ddPCR）实验验证了所鉴定的 AS 事件中的 4 个。几个基因中的 AS 事件与基因表达的变化相关。例如，在弥漫性病变动物的 ICV 中，与内吞作用、抗原加工和呈递、补体激活以及人类的几种炎症和自身免疫性疾病相关的基因的表达变化相关的可变剪接基因。总之，我们的研究结果确定了 AS 参与 PTB 和人类疾病发病机制的常见机制，并为控制这些疾病的新的诊断和治疗干预措施提供了依据。
