RNA Biology Laboratory, Department of Chemistry, Indian Institute of Technology Delhi, India.
FEBS Lett. 2024 May;598(9):1034-1044. doi: 10.1002/1873-3468.14882. Epub 2024 Apr 19.
MTS1338, a distinctive small RNA in pathogenic mycobacteria, plays a crucial role in host-pathogen interactions during infection. Mycobacterial cells encounter heterogeneous stresses in macrophages, which highly upregulate MTS1338. A dormancy regulatory factor DosR regulates the intracellular abundance of MTS1338. Herein, we investigated the interplay of DosR and a low pH-inducible gene regulator PhoP binding to the MTS1338 promoter. We identified that DosR strongly binds to two regions upstream of the MTS1338 gene. The proximal region possesses a threefold higher affinity than the distal site, but the presence of both regions increased the affinity for DosR by > 10-fold. PhoP did not bind to the MTS1338 gene but binds to the DosR-bound MTS1338 gene, suggesting a concerted mechanism for MTS1338 expression.
MTS1338 是一种在致病性分枝杆菌中独特的小 RNA，在感染期间的宿主-病原体相互作用中发挥关键作用。分枝杆菌细胞在巨噬细胞中遇到异质应激，这会高度上调 MTS1338。休眠调节因子 DosR 调节 MTS1338 的细胞内丰度。在此，我们研究了 DosR 和低 pH 诱导的基因调节剂 PhoP 与 MTS1338 启动子结合的相互作用。我们发现 DosR 强烈结合在 MTS1338 基因的上游两个区域。近端区域的亲和力比远端位点高三倍，但两个区域的存在使 DosR 的亲和力增加了 >10 倍。PhoP 不结合 MTS1338 基因，但结合 DosR 结合的 MTS1338 基因，这表明 MTS1338 表达的协同机制。
