Self-regulatory function of bacterial small heat shock protein IbpA through mRNA binding is conferred by a conserved arginine

Abstract

Bacterial small heat shock proteins, IbpA and IbpB, co-aggregate with denatured proteins and recruit other chaperones for the processing of aggregates, thereby assisting in their refolding. In addition, as a recently revealed uncommon feature, Escherichia coli IbpA self-represses its own translation through interaction with the 5' untranslated region (UTR) of the ibpA mRNA, enabling IbpA to act as a mediator of negative feedback regulation. Although IbpA also suppresses the expression of IbpB, IbpB does not have the self-repression activity despite the two Ibps being highly homologous. This study demonstrates that the self-repression function of IbpA is conserved in other bacterial IbpAs. Moreover, a cationic residue-rich region in the alpha-crystallin domain (ACD) of IbpA, which is not conserved in IbpB, is critical for the self-suppression activity. Notably, arginine 93 (R93) located within the ACD is an essential residue that cannot be replaced by the other 19 amino acids, including lysine. IbpA-R93 mutants completely lost the interaction with the 5' UTR of the ibpA mRNA but retained almost all of the chaperone activity to sequester denatured proteins. Taken together, the conserved Arg93-mediated translational control of IbpA through RNA binding would be beneficial for a rapid and massive supply of the chaperone on demand.