Analysis of A. thaliana Hsp40s further supports prion‐specific domain‐based functions and primacy of the glycine‐rich region in [ RNQ + ]/[ PIN + ] propagation

Amyloid‐based prions of the baker’s yeast, Saccharomyces cerevisiae rely upon fragmentation by the chaperone machinery for propagation in cell populations. In addition to Hsp104 and Hsp70, the Hsp40 Sis1 is specifically essential for prion propagation, yet different prions rely upon distinct parts of Sis1. We recently identified six functional orthologs of Sis1 in the model plant Arabidopsis thaliana which rescue both cell viability and strong [ PSI + ] propagation in a Δ sis1 strain, however these orthologs vary in their ability to maintain [ RNQ + ]/[ PIN + ] and weak variants of [ PSI + ]. Despite high sequence homology among the six A. thaliana paralogs, significant differences in the glycine‐rich regions exist. This region of Sis1 is universally required for the propagation of all known variants of [ RNQ + ], though its role in weak [ PSI + ] propagation in less clear. Here we report the results of a domain‐based analysis utilizing chimeric forms of two orthologs and validated in two distinct yeast strain backgrounds. Our data indicate that the glycine‐rich region specifies the propagation of [ RNQ + ] but not weak [ PSI + ], as no change in weak [ PSI + ] propagation was observed. Support or Funding Information This work was supported by the Lafayette College Chemistry Department, the EXCEL research scholarship program ( www.lafayette.edu ), the National Institute of General Medical Sciences of the National Institutes of Health under Award Number R15GM110606, and the Henry Dreyfus Teacher Scholar Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Dreyfus Foundation.