Stresses that Raise Np₄A Levels Induce Protective Nucleoside Tetraphosphate Capping of Bacterial RNA

Present in all realms of life, dinucleoside tetraphosphates (Np₄Ns) are generally considered signaling molecules. However, only a single pathway for Np₄N signaling has been delineated in eukaryotes, and no receptor that mediates the influence of Np₄Ns has ever been identified in bacteria. Here we show that, under disulfide stress conditions that elevate cellular Np₄N concentrations, diverse Escherichia coli mRNAs and sRNAs acquire a cognate Np₄ cap. Purified E. coli RNA polymerase and lysyl-tRNA synthetase are both capable of adding such 5′ caps. Cap removal by either of two pyrophosphatases, ApaH or RppH, triggers rapid RNA degradation in E. coli. ApaH, the predominant decapping enzyme, functions as both a sensor and an effector of disulfide stress, which inactivates it. These findings suggest that the physiological changes attributed to elevated Np₄N concentrations in bacteria may result from widespread Np₄ capping, leading to altered RNA stability and consequent changes in gene expression.