[PSI+]: An epigenetic modulator of translation termination efficiency

The [PSI+] factor of the yeast Saccharomyces cerevisiae is an epigenetic re gulator of translation termination. More than three decades ago, genetic an alysis of the transmission of [PSI+].revealed a complex and often contradic tory series of observations. However, many of these discrepancies may now b e reconciled by a revolutionary hypothesis: protein conformation-based inhe ritance (the prion hypothesis). This model predicts that a single protein c an stably exist in at least two distinct physical states, each associated w ith a different phenotype. Propagation of one of these traits is achieved b y a self-perpetuating change in the protein from one form to the other. Mou nting genetic and biochemical evidence suggests that the determinant of [PS I+] is the nuclear encoded Sup35p, a component of the translation terminati on complex. Here we review the series of experiments supporting the yeast p rion hypothesis and provide another look at the 30 years of work preceding this theory in light of our current state of knowledge.