An interchangeable prion-like domain is required for Ty1 retrotransposition.

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• Retrotransposons, like Ty1 in Saccharomyces cerevisiae, are mobile genetic elements that influence genome evolution.
• The assembly of Ty1 virus-like particles (VLPs) occurs in cytosolic foci called retrosomes, but the underlying mechanisms are not fully understood.

Purpose of the Study:

• To investigate the role of a novel intrinsically disordered N-terminal prion-like domain (PrLD) in the Ty1 Gag protein.
• To determine if this PrLD is essential for Ty1 retrotransposition and VLP assembly.
• To establish a versatile in vivo system for studying prion-like domains.

Main Methods:

• Deletion analysis of the Ty1 Gag PrLD.
• Construction and analysis of Ty1 Gag chimeras with heterologous prionogenic domains (yeast Sup35, mouse PrP).
• Assessment of VLP assembly, retrosome formation, and retrotransposition efficiency in vivo.

Main Results:

• The Ty1 Gag PrLD is required for efficient VLP assembly and retrotransposition.
• Deletion of the PrLD leads to severe defects in these processes without affecting Gag protein levels.
• Heterologous prion domains, including yeast Sup35 and mouse PrP, can functionally substitute for the Ty1 PrLD, supporting VLP assembly and retrotransposition.

Conclusions:

• The Ty1 PrLD is a key functional domain mediating essential steps in retrotransposition.
• The Ty1 system provides a powerful platform for studying the function of prion-like domains in vivo.
• Prion-like domains may be more widespread in mobile genetic elements than previously recognized.