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Host factor RBMX2 promotes epithelial cell apoptosis by downregulating APAF-1’s Retention Intron after Mycobacterium bovis infection

Authors :
Chao Wang
Yanzhu Jiang
Zhiming Yang
Haojun Xu
Abdul Karim Khalid
Tahira Iftakhar
Yongchong Peng
Lu Lu
Lei Zhang
Luiz Bermudez
Aizhen Guo
Yingyu Chen
Source :
Frontiers in Immunology, Vol 15 (2024)
Publication Year :
2024
Publisher :
Frontiers Media S.A., 2024.

Abstract

The Mycobacterium tuberculosis variant bovis (M. bovis) is a highly pathogenic environmental microorganism that causes bovine tuberculosis (bTB), a significant zoonotic disease. Currently, “test and culling” is the primary measure for controlling bTB, but it has been proven to be inadequate in animals due to their high susceptibility to the pathogen. Selective breeding for increased host resistance to bTB to reduce its prevalence is feasible. In this study, we found a vital host-dependent factor, RBMX2, that can potentially promote M. bovis infection. By knocking RBMX2 out, we investigated its function during M. bovis infection. Through transcriptome sequencing and alternative splicing transcriptome sequencing, we concluded that after M. bovis infection, embryo bovine lung (EBL) cells were significantly enriched in RNA splicing associated with apoptosis compared with wild-type EBL cells. Through protein/molecular docking, molecular dynamics simulations, and real-time quantitative PCR, we demonstrated that RBMX2 promotes the apoptosis of epithelial cells by upregulating and binding to apoptotic peptidase activating factor 1 (APAF-1), resulting in the alternative splicing of APAF-1 as a retention intron. To our knowledge, this is the first report of M. bovis affecting host epithelial cell apoptosis by hijacking RBMX2 to promote the intron splicing of downstream APAF-1. These findings may represent a significant contribution to the development of novel TB prevention and control strategies.

Details

Language :
English
ISSN :
16643224
Volume :
15
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.4d4e1382616549f8908b458a65673cb8
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2024.1431207