A regulatory role of the Rnq1 nonprion domain for prion propagation and polyglutamine aggregates.
Prions are infectious, self-propagating protein conformations. Rnq1 is required for the yeast Saccharomyces cerevisiae prion [PIN(+)], which is necessary for the de novo induction of a second prion, [PSI(+)]. Here we isolated a [PSI(+)]-eliminating mutant, Rnq1Delta100, that deletes the nonprion domain of Rnq1. Rnq1Delta100 inhibits not only [PSI(+)] prion propagation but also [URE3] prion and huntingtin's polyglutamine aggregate propagation in a [PIN(+)] background but not in a [pin(-)] background. Rnq1Delta100, however, does not eliminate [PIN(+)]. These findings are interpreted as showing a possible involvement of the Rnq1 prion in the maintenance of heterologous prions and polyQ aggregates. Rnq1 and Rnq1Delta100 form a sodium dodecyl sulfate-stable and Sis1 (an Hsp40 chaperone protein)-containing coaggregate in [PIN(+)] cells. Importantly, Rnq1Delta100 is highly QN-rich and prone to self-aggregate or coaggregate with Rnq1 when coexpressed in [pin(-)] cells. However, the [pin(-)] Rnq1-Rnq1Delta100 coaggregate does not represent a prion-like aggregate. These findings suggest that [PIN(+)] Rnq1-Rnq1Delta100 aggregates interact with other transmissible and nontransmissible amyloids to destabilize them and that the nonprion domain of Rnq1 plays a crucial role in self-regulation of the highly reactive QN-rich prion domain of Rnq1.
Kurahashi
Hiroshi
H
Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Ishiwata
Masao
M
Shibata
Shoichiro
S
Nakamura
Yoshikazu
Y
D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004271:DNA, Fungal / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D046912:Multiprotein Complexes; D010454:Peptide Termination Factors; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion
D017931:DNA Primers; D004271:DNA, Fungal; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D046912:Multiprotein Complexes; D010454:Peptide Termination Factors; D010455:Peptides; D011328:Prions; C404807:RNQ1 protein, S cerevisiae; C070320:SIS1 protein, S cerevisiae; C068068:SUP35 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C097188:polyglutamine