Discovery of a role for the single START-domain protein Mtsp17 in transcriptional regulation

Abstract

Background Tuberculosis caused by the pathogen Mycobacterium tuberculosis (MTB), remains a significant threat to global health. Elucidating the mechanism of essential MTB genes will provide a theoretical basis for drug exploitation. Gene mtsp17 is essential and conserved in the Mycobacterium genus. Although the structure of Mtsp17 exhibits as a typical steroidogenic acute regulatory protein-related lipid transfer (START) family protein, its biological function is different from other START proteins. This study characterized the transcriptomes of Mycobacterium smegmatis to address the problem how suppressing mtsp17 reduces bacterial growth rate. Results 3% down- and 1% up-regulated protein-coding genes were significantly differentiated expressed by suppressing mtsp17 gene. Among them, desA1, an essential gene involved in mycolic acid synthesis, was found to be significantly depressed (3.1-fold). Further analyses showed that mstp17 can activate desA1 to regulate the bacterial growth. In addition, the anti-anti-SigF gene was dramatically decreased (8.9-fold) and 70 of the 79 differentially expressed genes showed the same change trends in the SigF knockout strain. The data indicate that Mtsp17 regulates SigF regulon by modulating mRNA abundance of the anti-sigma factor antagonist. Conclusions Our findings discover the role of Mtsp17 in transcriptional regulation that was unknown before, which provides new insights into the molecular mechanisms of START family and introduces a new node to the regulatory network of mycobacteria.