[PHI+], a novel Sup35-prion variant propagated with non-Gln/Asn oligopeptide repeats in the absence of the chaperone protein Hsp104.
BACKGROUND
The [PSI+] element of the budding yeast is an aggregated form of the translation release factor Sup35 that is propagated and transmitted cytoplasmically in a manner analogous to that of mammalian prions. The N-terminal of Sup35, necessary for [PSI+], contains oligopeptide repeats and multiple Gln/Asn residues.


RESULTS
We replaced the Gln/Asn-rich prion repeats of Sup35 with non-Gln/Asn repeats from heterologous yeast strains. These non-Gln/Asn repeat Sup35s propagated a novel [PSI+] variant, [PHI+], that appeared de novo 103 times more frequent than [PSI+]. [PHI+] was stably inherited in a non-Mendelian fashion, but not eliminated upon the inactivation of Hsp104, unlike known [PSI+] elements. In vitro, non-Gln/Asn repeat domains formed amyloid fibres that were shorter and grew more slowly than did Gln/Asn-rich prion domains, while [PHI+] aggregates were smaller than [PSI+] aggregates in vivo.


CONCLUSIONS
These findings suggest the existence of an alternative, Hsp104-independent pathway to replicate non-Gln/Asn variant Sup35 prion seeds.
Crist
Colin G
CG
Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Nakayashiki
Toru
T
Kurahashi
Hiroshi
H
Nakamura
Yoshikazu
Y
D000595:Amino Acid Sequence; D001216:Asparagine / Q000737:chemistry*; D001483:Base Sequence; D017931:DNA Primers; D005998:Glycine / Q000737:chemistry*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010454:Peptide Termination Factors; D011328:Prions / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D006360:Heat-Shock Proteins; D010454:Peptide Termination Factors; D011328:Prions; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D001216:Asparagine; D005998:Glycine