New & Noteworthy

Prions Let Yeast Take Traits for a Test Drive

August 27, 2012

For the most part, prions have a bad rep. They are the proverbial bad apple that spoils the whole bunch.

One bad apple can spoil the whole bunch...

Like a bad apple, a prion can "spoil" other proteins.

A prion is a protein that misfolds in a certain way that creates a chain reaction to misfold many additional copies of that particular protein in a cell. This misfolding en masse can cause severe problems like mad cow disease or Alzheimer’s.

As if that weren’t bad enough, this misfoldedness can spread from one organism to another. Once a prion gets into a cell and/or a part of the body, it will cause many of its properly folded brethren to misfold too. This is true even though the prion gene in the new host is happily churning out properly folded protein.

These things look like a nightmare. Why on Earth are prions still around? Because in addition to their bad side, they can sometimes be an advantage too (at least in yeast).

In a study published in Nature in February 2012, Halfmann and coworkers provide compelling evidence that prions can help both laboratory and wild yeast strains to adapt rapidly to a changing environment, by unlocking survival traits hidden in yeast DNA. In other words, prions are a way for a yeast population to hedge its bets against a world of changing environments.

The authors focused on the most famous prion in yeast, the translation termination protein Sup35p. When Sup35p switches to prion mode ([PSI+]), it becomes bound up in insoluble fibers, causing translation termination to become leaky. Now normally untranslated parts of mRNAs become part of their respective proteins. And this can change these proteins’ functions.

Sure, most of this newfound variation will have no effect or maybe even be harmful, but occasionally the prion will reveal a beneficial trait. This yeast can then go on to survive and even thrive in this new environment.

This mechanism may apply to other prions in addition to Sup35p. Prions tend to come from proteins that are global regulators of transcription or translation. In the non-prion form, these proteins do their usual job making sure transcription and translation are following the rules. But when these proteins become misfolded into a prion, they can no longer perform their usual function. This uncovers previously silent bits of DNA or RNA for transcription or translation.

These authors also convincingly showed that prions are not some weird phenomenon found only in laboratory strains of yeast. They found evidence for prions in 255 out of the 690 wild strains they surveyed (although only ten had Sup35p based prions). Not only that, but many of these prions also conferred new traits on the yeast that could be beneficial in certain circumstances. It looks like prions may serve an important function in yeast.

A more surprising result from the study is that these prion-derived traits carry on in later generations even after the prion has been removed. For example, the authors looked at the wine yeast UCD978. They found that when Sup35p was in its prion form in this strain, UCD978 could effectively penetrate agar surfaces and that this trait was lost when the prion was cured, reverting Sup35p to its functional form.

They then took the study further and showed that after meiosis and sporulation, 5/30 haploid progeny of UCD978 retained the trait even after the prion was removed. These five had fixed the new trait and no longer required the prion to maintain it. They got all the benefits with none of the costs.

It isn’t obvious how this trait became independent of the original inducing prion. But that is for another study (or two or ten).

If the results of this study pan out, they show that prions are not just part of a disease but are really just another way to adapt to environmental changes and to pass them down to future generations. Maybe these apples aren’t so bad after all!

Prions allow yeast cells to take various traits out for a test drive.