A_small_protein_regulates_cell_division

Small proteins constitute a mysterious fraction of cellular proteins, and very little is known of their roles in Archaea. We identified a gene (cdrS) encoding a small protein in the model archaeon Haloferax volcanii that is highly transcribed and was essential. CRISPRi-mediated repression of cdrS caused slow growth, cell division defects, and changed the expression of multiple genes and their products associated with cell division, proteasomes and metabolism. ChIP-Seq identified 18 DNA-binding sites of the CdrS protein including one upstream of the promoter for diadenylate cyclase, which is required for essential c-di-AMP signalling. Finally, overexpression of cdrS also inhibited cell division, whereas cells over-expressing the operon containing cdrS and a homolog of the bacterial cell division protein ftsZ stimulated division. These findings suggest that coordinated activity of regulatory and mechanistic functions of these two proteins plays a central role in the regulation of euryarchaeal cell division.