New & Noteworthy

P is for Protection (not Processing)

January 11, 2013

Growing and dividing are dangerous work for a cell. Making all that energy throws off free radicals that mutate DNA and wreak havoc with delicate intracellular machinery. Given this it might seem surprising that just sitting there, not growing, is dangerous too. And yet it looks like it is.

Mr. Peabody and Sherman

Just as Mr. Peabody is always looking out for Sherman, so too are our P-bodies looking out for us.

When a cell runs out of food and goes into a quiescent state, it creates ribonucleoprotein (RNP) complexes called processing bodies (P bodies). In a new study out in GENETICS, Shah and colleagues were able to control how well yeast cells could make these P bodies. What they found was that cells that had trouble making P bodies didn’t survive the quiescent state as well as those cells that were great P body makers. It looked like P bodies were doing something to protect the cell when it wasn’t growing. In other words, being quiescent is dangerous too.

The key discovery made by the authors that allowed them to do these experiments was the fact that the Ras/PKA signaling system works specifically through the Pat1 protein to make P bodies. So by controlling the sensitivity of Pat1p to the signaling system, they could control the number of P bodies in the cell.

The Ras/PKA pathway phosphorylates two serine residues on Pat1p. When they are phosphorylated, P bodies are disrupted and/or are prevented from forming. The Pat1-EE mutation replaces the serine residues with glutamic acids, mimicking the phosphorylated state. The authors found that yeast cells carrying Pat1-EE produced fewer, smaller P bodies than did yeast carrying the wild type version of Pat1.

The authors then used this constitutively active mutant to ask whether P bodies helped cells survive the quiescent state. They compared the survival rate of cells carrying either the wild type version or the Pat1-EE protein and found that cells carrying the wild type version of Pat1 were more likely to survive after quiescence than were those cells carrying the constitutive form. More P bodies led to better survival.

The authors don’t yet know why this is, but one idea is that proteins and RNAs critical for survival after quiescence are stored in these particles. The idea would be that cells that have these key components squirreled away and protected survive better than those cells where these proteins and RNAs have degraded.

As a final point, it is important to mention why this matters (besides the excitement of figuring out how things work). Quiescent yeast cells are used as models for aging in higher eukaryotes like us. Perhaps by understanding how to make a yeast cell better survive this non-growing state, we can learn something about how to make people live longer too.

by D. Barry Starr, Ph.D., Director of Outreach Activities, Stanford Genetics