The chaperone Tsr2 regulates Rps26 release and reincorporation from mature ribosomes to enable a reversible, ribosome-mediated response to stress

Abstract

Although ribosome assembly is quality controlled to maintain protein homeostasis, different ribosome populations have been described. How these form, especially under stress conditions that impact energy levels and stop the energy-intensive production of ribosomes, remains unknown. Here we demonstrate how a physiologically relevant ribosome population arises during high Na+ and pH stress via dissociation of Rps26 from fully assembled ribosomes to enable a translational response to these stresses. The chaperone Tsr2 releases Rps26 in the presence of high Na or pH in vitro and is required for Rps26 release in vivo. Moreover, Tsr2 stores free Rps26 and promotes re-incorporation of the protein, thereby repairing the subunit after the stress subsides. Our data implicate a residue in Rps26 involved in Diamond Blackfan Anemia in mediating the effects of Na+. These data demonstrate how different ribosome populations can arise rapidly, without major energy input, and without bypass of quality control mechanisms. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/438496v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@151e234org.highwire.dtl.DTLVardef@d9d3fcorg.highwire.dtl.DTLVardef@ec628corg.highwire.dtl.DTLVardef@13a0917_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LITsr2 releases Rps26 from mature ribosomes to remodel ribosome populations C_LIO_LITsr2 stores released Rps26 and allows for ribosome repair after stress C_LIO_LIRps26 exploits a Mg binding site linked to Diamond Blackfan Anemia (DBA) C_LIO_LIChaperone-mediated ribosome remodeling might be common for chaperoned RPs C_LI