title: A bipolar functionality of Q/N-rich proteins: Lsm4 amyloid causes clearance of yeast prions.
abstract: Prions are epigenetic modifiers that cause partially loss-of-function phenotypes of the proteins in Saccharomyces cerevisiae. The molecular chaperone network that supports prion propagation in the cell has seen a great progress in the last decade. However, the cellular machinery to activate or deactivate the prion states remains an enigma, largely due to insufficient knowledge of prion-regulating factors. Here, we report that overexpression of a [PSI(+) ]-inducible Q/N-rich protein, Lsm4, eliminates the three major prions [PSI(+) ], [URE3], and [RNQ(+) ]. Subcloning analysis revealed that the Q/N-rich region of Lsm4 is responsible for the prion loss. Lsm4 formed an amyloid in vivo, which seemed to play a crucial role in the prion elimination. Fluorescence correlation spectroscopy analysis revealed that in the course of the Lsm4-driven [PSI(+) ] elimination, the [PSI(+) ] aggregates undergo a size increase, which ultimately results in the formation of conspicuous foci in otherwise [psi(-) ]-like mother cells. We also found that the antiprion activity is a general property of [PSI(+) ]-inducible factors. These data provoked a novel "unified" model that explains both prion induction and elimination by a single scheme.
authors.affiliation: Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Oishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Chan-Gi
authors.initials: CG
authors.lastname: Pack
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sako
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D004252:DNA Mutational Analysis; D011328:Prions / Q000378:metabolism*; D017414:Ribonucleoprotein, U4-U6 Small Nuclear / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000682:Amyloid; C093543:LSM4 protein, S cerevisiae; D011328:Prions; D017414:Ribonucleoprotein, U4-U6 Small Nuclear; D029701:Saccharomyces cerevisiae Proteins