More than Just a Phase: Prions at the Crossroads of Epigenetic Inheritance and Evolutionary Change

Journal of Molecular Biology
Anupam K Chakravarty, Daniel F Jarosz

Abstract

A central tenet of molecular biology is that heritable information is stored in nucleic acids. However, this paradigm has been overturned by a group of proteins called "prions." Prion proteins, many of which are intrinsically disordered, can adopt multiple conformations, at least one of which has the capacity to self-template. This unusual folding landscape drives a form of extreme epigenetic inheritance that can be stable through both mitotic and meiotic cell divisions. Although the first prion discovered-mammalian PrP-is the causative agent of debilitating neuropathies, many additional prions have now been identified that are not obviously detrimental and can even be adaptive. Intrinsically disordered regions, which endow proteins with the bulk property of "phase-separation," can also be drivers of prion formation. Indeed, many protein domains that promote phase separation have been described as prion-like. In this review, we describe how prions lie at the crossroads of phase separation, epigenetic inheritance, and evolutionary adaptation.

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Citations

Mar 17, 2019·International Journal of Molecular Sciences·Anne H S MartinelliRodrigo Ligabue-Braun
Feb 13, 2019·Cold Spring Harbor Perspectives in Biology·James Shorter, Daniel R Southworth
Nov 22, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Antonio MagrìDiego La Mendola
Jun 5, 2019·Nature Communications·Alexandrea N RizoDaniel R Southworth
Sep 12, 2018·International Journal of Molecular Sciences·Claudia CampanellaAntonio Palumbo Piccionello
Feb 26, 2019·Microbial Biotechnology·Grégory BoëlAntoine Danchin
Feb 21, 2019·Proceedings of the National Academy of Sciences of the United States of America·Eleanor FlemingAnn Hochschild
Nov 24, 2019·Molecular Cell·Anupam K ChakravartyDaniel F Jarosz
Nov 4, 2020·ELife·Shan JiangBeidong Liu
Jan 16, 2021·Trends in Biochemical Sciences·Bede PortzJames Shorter
Jun 3, 2021·Journal of Developmental Biology·Rwik Sen, Christopher Barnes
May 25, 2021·Integrative and Comparative Biology·Edmund D BrodieNicole C Riddle
Aug 28, 2021·Journal of Molecular Biology·Jan S FasslerBryan T Phillips

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