A Mycobacterium tuberculosis secreted virulence factor Rv1435c/hsr1 disrupts host snRNP biogenesis

• 成果类型: Article
• 署名作者: Chauhan, Komal; Datta, Dipanwita; Kapoor, Yogita; Passricha, Nishat; Dutt, Ravi; Arora, Naresh; Das, Mrinmoy; Rao, Kavya; Singh, Lakshyaveer; Gautam, Arunima; Sharma, Raman Deep; Sarkar, Binayak; Yadav, Mohit; Malakar, Basanti; Kalam, Haroon; Saini, Prince; Mehra, Lalita; Das, Prasenjit; Ahuja, Vineet; Singhal, Amit; Nandicoori, Vinay; Kumar, Dhiraj
• 署名单位: Department of Biotechnology (DBT) India; International Center for Genetic Engineering & Biotechnology (ICGEB); International Center for Genetic Engineering & Biotechnology (ICGEB), New Delhi; Council of Scientific & Industrial Research (CSIR) - India; CSIR - Centre for Cellular & Molecular Biology (CCMB); Academy of Scientific & Innovative Research (AcSIR); Department of Biotechnology (DBT) India; National Institute of Immunology (NII); Indian Institute of Science Education & Research (IISER) - Mohali; All India Institute of Medical Sciences (AIIMS) New Delhi; All India Institute of Medical Sciences (AIIMS) New Delhi; Agency for Science Technology & Research (A*STAR); A*STAR Infectious Diseases Labs (A*STAR IDL); Agency for Science Technology & Research (A*STAR); A*STAR - Singapore Immunology Network (SIgN)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-10779
• DOI: 10.1073/pnas.2423349122
• 发表日期: 2025-07-02
• 关键词: gene-expression; smn complex; u-snrnp; splicing regulation; protein; responses; LIFE

摘要

Transcriptional adaptation drives the host responses to Mycobacterium tuberculosis (Mtb) the mechanism for which remains unknown. Here, we report a mechanism whereby a secreted Mtb protein interferes with the biogenesis of key spliceosomal components. A ing with the host RNA splicing factors (SFs). Through custom- designed in- cell assays, between Mtb phagosomes and U5 snRNA and SNRPF, key components of the snRNPs. Genetic deletion of Rv1435c/hsr1 reverses the specific exon- skipping events caused by tion in macrophages and in vivo infection in mice. Tissue sections from the WT Mtb or also noted in the human intestinal tuberculosis (ITB) biopsies. Thus, hsr1 is a virulence from the host and pathogen are novel targets for antituberculosis therapy.