Alternative splicing of pre-mRNA modulates the immune response in Holstein cattle naturally infected with Mycobacterium avium subsp. paratuberculosis

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...

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Bibliographic Details
Published in:Frontiers in immunology 2024-03, Vol.15, p.1354500
Main Authors: Badia-Bringué, Gerard, Lavín, José Luis, Casais, Rosa, Alonso-Hearn, Marta
Format: Article
Language:English
Subjects:
Alternative Splicing
Animals
autoimmune diseases
Cattle
chronic inflammatory diseases
Humans
Immunity
molecular mechanisms
Mycobacterium avium subsp. paratuberculosis
paratuberculosis
Paratuberculosis - genetics
RNA Precursors - genetics
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Summary: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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2024.1354500