Published on Sept. 1, 2019 in Mol Cell volume 75, 5.
PubMed ID: 31178354
Present in all realms of life, dinucleoside tetraphosphates (NpNs) are generally considered signaling molecules. However, only a single pathway for NpN signaling has been delineated in eukaryotes, and no receptor that mediates the influence of NpNs has ever been identified in bacteria. Here we show that, under disulfide stress conditions that elevate cellular NpN concentrations, diverse Escherichia coli mRNAs and sRNAs acquire a cognate Np cap. Purified E.\xa0coli 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.\xa0coli. 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 NpN concentrations in bacteria may result from widespread Np capping, leading to altered RNA stability and consequent changes in gene expression.