Diverse roles of the conserved ribosome-binding protein RsfS in bacterial physiology

Ribosomes are essential macromolecules that convert mRNA to polypeptides. Ribosomes can be regulated by multiple mechanisms, including limiting the biogenesis of ribosomal subunits, sequestering 70S ribosomes, dimerizing 70S complexes into inactive 100S ribosomes, and “silencing” the 50S subunit to prevent the assembly of active 70S ribosomes. In this review, we focus on the protein that carries out ribosomal silencing, called ribosomal silencing factor S (RsfS), that has been shown in multiple species to bind to the uL14 ribosomal protein in the 50S subunit and prevent 50S-to-30S subunit joining. RsfS is a highly conserved small protein found across most bacterial species and in eukaryotes. The direct target of RsfS, uL14 ( rplN ), is one of the most conserved ribosomal proteins. RsfS has been primarily studied for binding interactions with uL14 and the downstream effects of preventing 70S ribosome assembly. rsfS null mutant strains exhibit defects in several bacterial species in vitro (stationary phase, biofilm, growth, nutrient limitation, and oxidative stress) and in vivo (macrophage and murine models). However, other topics remain underexplored, highlighting areas for future study, such as the regulation of RsfS and uL14 expression, additional roles in antibiotic tolerance, whether RsfS has physiological roles beyond ribosomal silencing, and if other factors dictate ribosomal interactions. Overall, while RsfS is clearly important in many bacteria, there remain many areas for future studies.