Non-coding RNAs play pivotal roles in bacterial signaling. However, RNAs from certain phyla (specially high-GC actinobacteria) still remain elusive. Here, by re-engineering the existing genome-wide search approach, we discover a family of structurally conserved RNAs that are present ubiquitously across actinobacteria, including mycobacteria. In vitro analysis shows that RNAs belonging to this family bind response-regulator proteins that contain the widely prevalent ANTAR domain. The Mycobacterium tuberculosis ANTAR protein gets phosphorylated by a histidine kinase and interacts with RNA only in its phosphorylated state. These newly identified RNAs reside only in certain transcripts and typically overlap with the ribosome-binding site, regulating translation of these transcripts. In this way, the RNAs directly link signaling pathways to translational control, thus expanding the mechanistic tool kit available for ANTAR-based control of gene expression. In mycobacteria, we find that RNAs targeted by ANTAR proteins majorly encode enzymes of lipid metabolism and associated redox pathways. This now allows us to identify the key genes that mediate ANTAR-dependent control of lipid metabolism. Our study establishes the identity and wide prevalence of ANTAR-target RNAs in mycobacteria, bringing RNA-mediated regulation in these bacteria to the center stage.

非编码 RNA 在细菌信号传导中起关键作用。然而，来自某些门（特别是高 GC 放线菌）的 RNA 仍然难以捉摸。在这里，通过重新设计现有的全基因组搜索方法，我们发现了一个结构上保守的 RNA 家族，它们普遍存在于包括分枝杆菌在内的放线菌中。体外分析表明，属于该家族的 RNA 与包含广泛流行的 ANTAR 结构域的反应调节蛋白结合。该结核杆菌ANTAR 蛋白被组氨酸激酶磷酸化，并仅与处于磷酸化状态的 RNA 相互作用。这些新发现的 RNA 仅存在于某些转录本中，并且通常与核糖体结合位点重叠，从而调节这些转录本的翻译。通过这种方式，RNA 直接将信号通路与翻译控制联系起来，从而扩展了可用于基于 ANTAR 的基因表达控制的机械工具包。在分枝杆菌中，我们发现 ANTAR 蛋白靶向的 RNA 主要编码脂质代谢酶和相关的氧化还原途径。这现在使我们能够确定介导 ANTAR 依赖性脂质代谢控制的关键基因。我们的研究确定了分枝杆菌中 ANTAR 目标 RNA 的特性和广泛流行，将这些细菌中 RNA 介导的调节带到了中心阶段。