Crist Colin G, Nakayashiki Toru, Kurahashi Hiroshi, Nakamura Yoshikazu
Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Genes Cells. 2003 Jul;8(7):603-18. doi: 10.1046/j.1365-2443.2003.00661.x.
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.
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.
These findings suggest the existence of an alternative, Hsp104-independent pathway to replicate non-Gln/Asn variant Sup35 prion seeds.
出芽酵母的[PSI+]元件是翻译释放因子Sup35的一种聚集形式，它以类似于哺乳动物朊病毒的方式在细胞质中传播和传递。Sup35的N端是[PSI+]所必需的，包含寡肽重复序列和多个Gln/Asn残基。
我们用来自异源酵母菌株的非Gln/Asn重复序列取代了Sup35富含Gln/Asn的朊病毒重复序列。这些非Gln/Asn重复序列的Sup35传播了一种新的[PSI+]变体[PHI+]，其出现频率比[PSI+]高103倍。[PHI+]以非孟德尔方式稳定遗传，但与已知的[PSI+]元件不同，在Hsp104失活后不会被消除。在体外，非Gln/Asn重复结构域形成的淀粉样纤维比富含Gln/Asn的朊病毒结构域更短且生长更慢，而在体内[PHI+]聚集体比[PSI+]聚集体更小。
这些发现表明存在一种独立于Hsp104的替代途径来复制非Gln/Asn变体Sup35朊病毒种子。
