Mycobacterial PstP impairs host RNA alternative splicing by dephosphorylation of spliceosome RBMX at S189
Abstract Mycobacterium tuberculosis (Mtb) infection significantly alters host cellular signaling and protein functions, facilitating immune evasion and intracellular survival. However, the molecular mechanisms underlying these interactions remain incompletely characterized. Here, we employed a multi...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-03-01
|
| Series: | iMetaOmics |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/imo2.53 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850190516491124736 |
|---|---|
| author | Tianxian Liu Jun‐Yu Xu Lei Zhao Yameng Fan Shuyu Xie Ke Ma Ying Zhou Minjia Tan Bang‐Ce Ye |
| author_facet | Tianxian Liu Jun‐Yu Xu Lei Zhao Yameng Fan Shuyu Xie Ke Ma Ying Zhou Minjia Tan Bang‐Ce Ye |
| author_sort | Tianxian Liu |
| collection | DOAJ |
| description | Abstract Mycobacterium tuberculosis (Mtb) infection significantly alters host cellular signaling and protein functions, facilitating immune evasion and intracellular survival. However, the molecular mechanisms underlying these interactions remain incompletely characterized. Here, we employed a multi‐omics strategy, including proteomics, phosphoproteomics, transcriptomics and interactomics, to investigate the impact of Mtb infection on host cellular processes. Our study revealed that mycobacteria modulate RNA alternative splicing in host cells by reducing the phosphorylation levels within the spliceosome complex. We identified the serine/threonine protein phosphatase (PstP) as a key effector, dephosphorylating the spliceosome RNA‐binding motif protein (RBMX) at the serine 189 site (S189). This modification influences the alternative splicing of PLA2G7, which encodes platelet‐activating factor acetylhydrolase, resulting an increase in the mRNA levels of a transcript containing exon9 (PLA2G7‐exon9+). Importantly, PLA2G7 isoform encoded by PLA2G7‐exon9+, in contrast to the isoform lacking exon9, acquires the ability to potentiate inflammatory responses. Collectively, our findings not only provide a comprehensive view of Mtb‐induced host regulatory networks but also elucidate a role for PstP in controlling a critical mediator of alterative splicing during infection. |
| format | Article |
| id | doaj-art-c71e20f1606043f2b56572f40efafddf |
| institution | OA Journals |
| issn | 2996-9506 2996-9514 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | iMetaOmics |
| spelling | doaj-art-c71e20f1606043f2b56572f40efafddf2025-08-20T02:15:16ZengWileyiMetaOmics2996-95062996-95142025-03-0121n/an/a10.1002/imo2.53Mycobacterial PstP impairs host RNA alternative splicing by dephosphorylation of spliceosome RBMX at S189Tianxian Liu0Jun‐Yu Xu1Lei Zhao2Yameng Fan3Shuyu Xie4Ke Ma5Ying Zhou6Minjia Tan7Bang‐Ce Ye8Laboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering East China University of Science and Technology Shanghai ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai ChinaLaboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering East China University of Science and Technology Shanghai ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai ChinaLaboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering East China University of Science and Technology Shanghai ChinaState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai ChinaLaboratory of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering East China University of Science and Technology Shanghai ChinaAbstract Mycobacterium tuberculosis (Mtb) infection significantly alters host cellular signaling and protein functions, facilitating immune evasion and intracellular survival. However, the molecular mechanisms underlying these interactions remain incompletely characterized. Here, we employed a multi‐omics strategy, including proteomics, phosphoproteomics, transcriptomics and interactomics, to investigate the impact of Mtb infection on host cellular processes. Our study revealed that mycobacteria modulate RNA alternative splicing in host cells by reducing the phosphorylation levels within the spliceosome complex. We identified the serine/threonine protein phosphatase (PstP) as a key effector, dephosphorylating the spliceosome RNA‐binding motif protein (RBMX) at the serine 189 site (S189). This modification influences the alternative splicing of PLA2G7, which encodes platelet‐activating factor acetylhydrolase, resulting an increase in the mRNA levels of a transcript containing exon9 (PLA2G7‐exon9+). Importantly, PLA2G7 isoform encoded by PLA2G7‐exon9+, in contrast to the isoform lacking exon9, acquires the ability to potentiate inflammatory responses. Collectively, our findings not only provide a comprehensive view of Mtb‐induced host regulatory networks but also elucidate a role for PstP in controlling a critical mediator of alterative splicing during infection.https://doi.org/10.1002/imo2.53inflammatory responseintegrative multi‐omic analysismycobacteriaPLA2G7RBMX S189RNA alternative splicing |
| spellingShingle | Tianxian Liu Jun‐Yu Xu Lei Zhao Yameng Fan Shuyu Xie Ke Ma Ying Zhou Minjia Tan Bang‐Ce Ye Mycobacterial PstP impairs host RNA alternative splicing by dephosphorylation of spliceosome RBMX at S189 iMetaOmics inflammatory response integrative multi‐omic analysis mycobacteria PLA2G7 RBMX S189 RNA alternative splicing |
| title | Mycobacterial PstP impairs host RNA alternative splicing by dephosphorylation of spliceosome RBMX at S189 |
| title_full | Mycobacterial PstP impairs host RNA alternative splicing by dephosphorylation of spliceosome RBMX at S189 |
| title_fullStr | Mycobacterial PstP impairs host RNA alternative splicing by dephosphorylation of spliceosome RBMX at S189 |
| title_full_unstemmed | Mycobacterial PstP impairs host RNA alternative splicing by dephosphorylation of spliceosome RBMX at S189 |
| title_short | Mycobacterial PstP impairs host RNA alternative splicing by dephosphorylation of spliceosome RBMX at S189 |
| title_sort | mycobacterial pstp impairs host rna alternative splicing by dephosphorylation of spliceosome rbmx at s189 |
| topic | inflammatory response integrative multi‐omic analysis mycobacteria PLA2G7 RBMX S189 RNA alternative splicing |
| url | https://doi.org/10.1002/imo2.53 |
| work_keys_str_mv | AT tianxianliu mycobacterialpstpimpairshostrnaalternativesplicingbydephosphorylationofspliceosomerbmxats189 AT junyuxu mycobacterialpstpimpairshostrnaalternativesplicingbydephosphorylationofspliceosomerbmxats189 AT leizhao mycobacterialpstpimpairshostrnaalternativesplicingbydephosphorylationofspliceosomerbmxats189 AT yamengfan mycobacterialpstpimpairshostrnaalternativesplicingbydephosphorylationofspliceosomerbmxats189 AT shuyuxie mycobacterialpstpimpairshostrnaalternativesplicingbydephosphorylationofspliceosomerbmxats189 AT kema mycobacterialpstpimpairshostrnaalternativesplicingbydephosphorylationofspliceosomerbmxats189 AT yingzhou mycobacterialpstpimpairshostrnaalternativesplicingbydephosphorylationofspliceosomerbmxats189 AT minjiatan mycobacterialpstpimpairshostrnaalternativesplicingbydephosphorylationofspliceosomerbmxats189 AT bangceye mycobacterialpstpimpairshostrnaalternativesplicingbydephosphorylationofspliceosomerbmxats189 |