Sup35

Sup35 is a gene in the budding yeast Saccharomyces cerevisiae that encodes the translation termination factor eRF3, also known as Sup35p. It functions with eRF1 (Sup45) to promote efficient termination at stop codons during translation. The protein comprises an N-terminal glutamine/asparagine-rich prion-forming domain, a central region, and a C-terminal GTPase domain responsible for interactions with eRF1 and for GTP-dependent termination activity.

Sup35 can exist in a soluble form and in a self-perpetuating prion state, designated [PSI+]. In the [PSI+] state, the N-terminal domain forms amyloid-like aggregates that sequester Sup35, reducing the level of functional termination factor and causing increased readthrough of stop codons. Consequently, yeast in [PSI+] display nonsense suppression, revealing phenotypes otherwise suppressed in [psi-]. The degree of suppression depends on prion strain and expression level.

Prion propagation is templated; existing aggregates promote conversion of soluble Sup35 into prion form. Propagation relies on the cellular chaperone machinery, particularly Hsp104, along with Hsp70 and Hsp40. Disruption of Hsp104 with guanidine hydrochloride (GuHCl) can cure [PSI+] by preventing prion propagation.

Sup35/[PSI+] serves as a widely used model system for studying prion biology, epigenetic inheritance, and protein-based inheritance in eukaryotes. The gene's products and regulation are specific to yeast; there is no direct pathogenic role in humans, though the general principles illuminate prion-like mechanisms in other organisms.