From Tuberculosis Bedside to Bench: UBE2B Splicing as a Potential Biomarker and Its Regulatory Mechanism

Authors

Mengyuan Lyu, Sichuan University
Jian Zhou, Sichuan University
Yanbing Zhou, Sichuan University
Weelic Chong, Thomas Jefferson UniversityFollow
Wei Xu, University of Toronto
Hongli Lai, Sichuan University
Lu Niu, Sichuan University
Yang Hai, Thomas Jefferson University Hospital
Xiaojun Yao, Public and Health Clinic Centre of Chengdu
Sheng Gong, Public and Health Clinic Centre of Chengdu
Qinglan Wang, Sichuan University
Yi Chen, Sichuan University
Yili Wang, Sichuan University
Liyu Chen, Sichuan University
Ganzi People's Hospital, Ganzi People's Hospital
Jiongjiong Zeng, Ganzi People's Hospital
Chengdi Wang, Sichuan University
Binwu Ying, Sichuan University

Document Type

Article

Publication Date

2-24-2023

Comments

This article is the author's final published version in Signal Transduction and Targeted Therapy, Volume 8, 2023, Article number 82.

The published version is available at https://doi.org/10.1038/s41392-023-01346-2. Copyright © The Author(s) 2023.

Abstract

Alternative splicing (AS) is an important approach for pathogens and hosts to remodel transcriptome. However, tuberculosis (TB)-related AS has not been sufficiently explored. Here we presented the first landscape of TB-related AS by long-read sequencing, and screened four AS events (S100A8-intron1-retention intron, RPS20-exon1-alternaitve promoter, KIF13B-exon4-skipping exon (SE) and UBE2B-exon7-SE) as potential biomarkers in an in-house cohort-1. The validations in an in-house cohort-2 (2274 samples) and public datasets (1557 samples) indicated that the latter three AS events are potential promising biomarkers for TB diagnosis, but not for TB progression and prognosis. The excellent performance of classifiers further underscored the diagnostic value of these three biomarkers. Subgroup analyses indicated that UBE2B-exon7-SE splicing was not affected by confounding factors and thus had relatively stable performance. The splicing of UBE2B-exon7-SE can be changed by heat-killed mycobacterium tuberculosis through inhibiting SRSF1 expression. After heat-killed mycobacterium tuberculosis stimulation, 231 ubiquitination proteins in macrophages were differentially expressed, and most of them are apoptosis-related proteins. Taken together, we depicted a global TB-associated splicing profile, developed TB-related AS biomarkers, demonstrated an optimal application scope of target biomarkers and preliminarily elucidated mycobacterium tuberculosis-host interaction from the perspective of splicing, offering a novel insight into the pathophysiology of TB.

Recommended Citation

Lyu, Mengyuan; Zhou, Jian; Zhou, Yanbing; Chong, Weelic; Xu, Wei; Lai, Hongli; Niu, Lu; Hai, Yang; Yao, Xiaojun; Gong, Sheng; Wang, Qinglan; Chen, Yi; Wang, Yili; Chen, Liyu; Ganzi People's Hospital; Zeng, Jiongjiong; Wang, Chengdi; and Ying, Binwu, "From Tuberculosis Bedside to Bench: UBE2B Splicing as a Potential Biomarker and Its Regulatory Mechanism" (2023). Student Papers, Posters & Projects. Paper 94.
https://jdc.jefferson.edu/student_papers/94

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Language

English