GENETICS EDITOR’S CHOICE
DM Garcia et al., “A prion accelerates proliferation at the expense of lifespan,” eLife, 10:e60917, 2021.
Not all inheritances are genetic. Proteins, which can assume different conformations, may provide another means of transmitting information between generations. David Garcia and colleagues at the University of Oregon recently identified more than 40 proteins that, when overexpressed, appear to induce heritable phenotypes in yeast (Saccharomyces cerevisiae) which can be reversed by other experimental manipulations.
Focusing on one protein, the RNA-modifying enzyme Pus4, the team determined that its overexpression led to faster growth and death of cells and their progeny. The researchers attributed these changes to a “protein-based element of inheritance”, which they named [BIG+]. Although the molecular details remain unclear, Garcia notes that the epigenetic inheritance of [BIG+] could help cells adjust their growth and proliferation according to the environment.
Randal Halfmann of the Stowers Institute, who was not involved in the work, says the results underscore the diversity of mechanisms of inheritance beyond DNA, noting that the team did “very thorough work to show that there is an epigenetic mechanism here”. It is unclear how Pus4 regulates growth changes, or why [BIG+]- which provides a growth advantage under laboratory conditions – is not the default state, he says, adding that he would be interested to see if the change can occur spontaneously. “More mechanistic studies will be needed to understand how it works.”
Halfmann, who does research on prions, says that although researchers describe [BIG+] as a prion, the evidence that it is one in the conventional sense – a misfolded protein that causes peptides of the same sequence to misfold in the same way – is weak. Garcia notes in an email that he defines prions more broadly, as any protein-based hereditary element, adding that there may be additional proteins and RNAs involved in mediating [BIG+]. “I think protein-based hereditary elements and ‘prions’ are really one and the same thing.”