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Expanding the CarD interaction network: CrsL is a novel transcription regulator in actinobacteria

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SHOMAN Mahmoud ČERNÝ Martin JIRAT MATEJCKOVA Jitka SCHWARZ Marek BORAH Nabajyoti VANKOVA HAUSNEROVA Viola NEVA Silvia SIKOVA Michaela SANDEROVA Hana HALADA Petr HUBALEK Martin DVORAKOVA Vera PREVOROVSKY Martin HOLUBOVA Jana STANEK Ondrej KRASNY Libor ŽÍDEK Lukáš HNILICOVA Jarmila

Rok publikování 2025
Druh Článek v odborném periodiku
Časopis / Zdroj NUCLEIC ACIDS RESEARCH
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www https://academic.oup.com/nar/article/53/22/gkaf1342/8382376
Doi https://doi.org/10.1093/nar/gkaf1342
Klíčová slova CarD; CrsL; Transcription regulation; Actinobacteria; Mycobacterium smegmatis; Mycobacterium tuberculosis; RNA polymerase
Přiložené soubory
Popis Bacterial transcription regulation is critical for adaptation and survival. CarD is an essential transcription factor in mycobacteria involved in the regulation of gene expression. We searched for CarD interaction partners in Mycobacterium smegmatis and identified a novel uncharacterized protein, named CrsL (MSMEG_5890). CrsL is a 5.7 kDa protein shown by NMR to be intrinsically disordered. CrsL homologs are present in actinobacteria, including pathogenic species such as Mycobacterium tuberculosis. CrsL interacts directly with CarD, adopting an ordered structure in the complex, and also binds RNAP, controlling CarD–RNAP association. ChIP-seq showed that CrsL associates with the promoters of actively transcribed genes and ~75% of these regions are also associated with CarD. RNA-seq revealed ~50% and ~66% overlap in differentially expressed genes between CrsL and CarD knockdowns during the exponential and stationary phases, respectively. Among CrsL-regulated genes are DesA desaturase (MSMEG_5773) and DEAD/DEAH-box RNA helicase MSMEG_1930, which contribute to cold stress adaptation. CrsL supports the growth of M. smegmatis at elevated temperature but limits growth in cold environments. In summary, these findings identify CrsL as a novel, conserved CarD-interacting protein playing a key role in mycobacterial stress responses by modulating CarD function.
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