Sup35Edit

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Sup35 is a gene in the budding yeast genus Saccharomyces that encodes a central translation termination factor. The protein product, often referred to as Sup35p, partners with Sup45p (the yeast eRF1) to recognize stop codons and terminate protein synthesis. In normal circumstances this partnership ensures accurate translation termination and proper proteome integrity for the cell. Sup35p is thus a key component of the cellular machinery that reads the genetic code and converts it into functional proteins. For broader context, see Saccharomyces cerevisiae and translation termination.

In addition to its canonical role in translation, Sup35p is the prototype protein in a widely studied class of heritable protein conformations known as prions. The Sup35 protein contains a long, glutamine- and asparagine-rich region at its N-terminus that can adopt an alternative, amyloid-forming conformation. When Sup35p adopts this prion form, the cellular pool of functional Sup35p is sequestered into aggregates, diminishing translation termination efficiency. In yeast, this prion state is denoted as PSI+ and represents a prime example of how protein conformation can influence gene expression and inheritance without changes to the underlying DNA.

Structure and function

  • Genetic encoding and protein architecture: The SUP35 gene encodes a protein with distinct domains. The C-terminal portion contains the GTPase-related features required for its role as a translation termination factor (often described as the eRF3 domain). The N-terminal region is unusually rich in glutamine and asparagine, a composition associated with prion-forming potential. The juxtaposition of a conventional eRF3-like core with a prion-prone N-terminal region explains both the normal termination activity and the prion biology of Sup35p. See eRF3 and Prion domain for related concepts.

  • Role in translation termination: Sup35p functions in concert with Sup45p (eRF1) to recognize stop codons in mRNA and promote release of the nascent polypeptide from the ribosome. The process involves GTP hydrolysis by the eRF3-like domain, synchronizing termination with ribosomal dynamics and ensuring fidelity of protein synthesis. See translation termination and eRF1.

  • Prion domain and amyloid formation: The N-terminal is capable of undergoing a conformational switch to an amyloid-like aggregate. This prion form is self-propagating and heritable through cell divisions. The transition from a soluble form to a prion aggregate alters the effective dosage of functional Sup35p in the cell, leading to measurable phenotypic consequences. See amyloid and Prion.

Prion biology and the PSI+ state

  • Formation and propagation: When Sup35p adopts the prion conformation, it forms aggregates that can be transmitted to daughter cells, thereby changing the state of translation termination within the lineage. The maintenance of the PSI+ state depends on cellular chaperones and disaggregases, notably Hsp104 among others, which regulate the size and number of aggregates and thus the heritability of the state.

  • Phenotypic consequences: The PSI+ state reduces the effective termination efficiency, causing increased read-through of stop codons in some transcripts. This can reveal cryptic or previously silent genetic variation, potentially altering phenotypes in a way that is measurable under laboratory conditions. Classic demonstrations of stop codon read-through and altered colony phenotypes have made PSI+ a hallmark example of prion biology in a model organism. See stop codon read-through and cryptic genetic variation.

  • Controversies and debates: The existence and biological significance of prions in yeast, including PSI+, have spurred ongoing discussion. Proponents argue that prions can serve as a bet-hedging mechanism, enabling phenotypic diversity in fluctuating environments, while skeptics question the frequency, adaptive value, and ecological relevance of prions in natural populations. Research continues to refine how frequently such states arise in wild strains versus laboratory conditions and what selective pressures, if any, favor prion maintenance. See prion and yeast genetics.

Evolutionary and practical implications

  • Modeling prion biology: Sup35p/[PSI+] provides a tractable system to study protein misfolding, amyloid formation, and epigenetic inheritance. The insights gained have informed broader understanding of prions across species and have helped illuminate how conformational states can transcend genetic changes to influence phenotype.

  • Relevance to biotechnology and genetics: Because PSI+ modulates translation termination, researchers can use Sup35p as a tool to explore gene expression regulation, translational recoding, and the emergence of phenotypic diversity. The interplay between Sup35p, its cofactors, and cellular chaperones also informs considerations about proteostasis and cellular stress responses in eukaryotes.

See also