The alarmones (p)ppGpp directly regulate translation initiation during entry into quiescence
Simon Diez, Jae-Wook Ryu, Kelvin Caban, Ruben L. Gonzalez, Jonathan Dworkin
Abstract
Significance All bacteria inevitably encounter conditions that are not conducive to growth and, in response, they can enter into quiescent phenotypes. The nucleotides guanosine tetraphosphate and pentaphosphate ((p)ppGpp) play a key role in this response by inhibiting DNA replication, GTP biosynthesis, and transcription. (p)ppGpp also mediates down-regulation of protein synthesis by reducing ribosome biogenesis. However, whether (p)ppGpp also regulates active translation, the most energy intensive process in the cell, during quiescence is not known. Here, we show that (p)ppGpp directly inhibits translation initiation when bacteria stop growing rapidly by binding the essential GTPase IF2. The present study identifies translation initiation as a regulatory target during quiescence in bacteria and establishes the mechanistic basis of this regulation.