Premium
Feedback control of prion formation and propagation by the ribosome‐associated chaperone complex
Author(s) -
Kiktev Denis A.,
Melomed Mikhail M.,
Lu Caroline D.,
Newnam Gary P.,
Chernoff Yury O.
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12960
Subject(s) - ribosome , biology , chaperone (clinical) , overproduction , microbiology and biotechnology , cytosol , yeast , translation (biology) , protein aggregation , biochemistry , rna , messenger rna , gene , medicine , pathology , enzyme
Summary Cross‐beta fibrous protein aggregates (amyloids and amyloid‐based prions) are found in mammals (including humans) and fungi (including yeast), and are associated with both diseases and heritable traits. The H sp104/70/40 chaperone machinery controls propagation of yeast prions. The H sp70 chaperones S sa and S sb show opposite effects on [ PSI + ], a prion form of the translation termination factor S up35 (e RF 3). S sb is bound to translating ribosomes via ribosome‐associated complex ( RAC ), composed of H sp40‐ Z uo1 and H sp70‐ S sz1. Here we demonstrate that RAC disruption increases de novo prion formation in a manner similar to S sb depletion, but interferes with prion propagation in a manner similar to S sb overproduction. Release of S sb into the cytosol in RAC ‐deficient cells antagonizes binding of S sa to amyloids. Thus, propagation of an amyloid formed because of lack of ribosome‐associated S sb can be counteracted by cytosolic S sb, generating a feedback regulatory circuit. Release of S sb from ribosomes is also observed in wild‐type cells during growth in poor synthetic medium. Ssb is, in a significant part, responsible for the prion destabilization in these conditions, underlining the physiological relevance of the S sb‐based regulatory circuit.