A distinct RNA recognition mechanism governs Np 4 decapping by RppH

Abstract

Significance Dinucleoside tetraphosphate alarmones function in bacteria as precursors to 5′-terminal nucleoside tetraphosphate (Np 4 ) caps, becoming incorporated at high levels into RNA during stress and thereby influencing transcript lifetimes. However, little is known about how these noncanonical caps are removed as a prelude to RNA degradation. Here, we report that the RNA pyrophosphohydrolase RppH assumes a leading role in decapping those transcripts under conditions of disulfide stress and that it recognizes Np 4 -capped 5′ ends by an unexpected mechanism, generating a triphosphorylated RNA intermediate that must undergo further deprotection by RppH to trigger degradation. These findings help to explain the uneven distribution of Np 4 caps on bacterial transcripts and have important implications for how gene expression is reprogrammed in response to stress.