ABOVE: The prion-like state of a protein called Pus4 (green) may allow epigenetic inheritance of different growth strategies in yeast cells (pictured in this micrograph). eLife, 10:e69199, 2021


Not all inheritance is genetic. Proteins, which can adopt different conformations, may offer another way for information to be passed between generations. The University of Oregon’s David Garcia and colleagues recently identified more than 40 proteins that, when overexpressed, seem to induce heritable phenotypes in yeast (Saccharomyces cerevisiae) that can be reversed by further experimental manipulation. 

Focusing on one protein, the RNA-modifying enzyme Pus4, the team determined that overexpressing it caused cells and their offspring to grow faster and die sooner. The researchers attributed these changes to a “protein-based element of inheritance,” which they named [BIG+]. While the molecular details remain unclear, Garcia notes that epigenetic inheritance of [BIG+] could help cells adjust their growth and proliferation depending on the environment.

The Stowers Institute’s Randal Halfmann, who was not involved in the work, says the findings underline the diversity of inheritance mechanisms beyond just DNA, noting that the team did “a very thorough job of showing there’s an epigenetic mechanism here.” It’s not clear how Pus4 regulates growth changes, nor why [BIG+]—which offers a growth advantage under lab conditions—isn’t the default state, he says, adding that he would be interested to see whether the change can occur spontaneously. “More mechanistic studies will be required to understand how this is working.” 

Halfmann, who researches prions, says that although the researchers describe [BIG+] as a prion, the evidence that it is one in the conventional sense—a misfolded protein that causes peptides with the same sequence to misfold the same way—is weak. Garcia notes in an email that he’s defining prions more broadly, as any protein-based element of inheritance, adding that there may be additional proteins and RNAs involved in mediating [BIG+]. “I think that protein-based elements of inheritance and ‘prions’ are really one and the same.”

D.M. Garcia et al., “A prion accelerates proliferation at the expense of lifespan,” eLife, 10:e60917, 2021.