Cis and trans interactions between genes encoding PAF1 complex and ESCRT machinery components in yeast

Area of Science:

• Molecular Biology
• Genetics
• Yeast Biology

Background:

• Saccharomyces cerevisiae is a key model organism for eukaryotic gene studies.
• Gene proximity in yeast can complicate genetic data interpretation, especially in high-throughput studies.
• The PAF1 complex influences RNA levels, histone modifications, and RNA processing, with links to cancer and telomere biology.
• The ESCRT-II complex (including Vps36) is involved in protein sorting for degradation.

Purpose of the Study:

• To investigate the interplay between the PAF1 complex and VPS36, an adjacent gene.
• To explore genetic interactions between PAF1 complex components and ESCRT machinery.
• To understand the impact of these interactions on telomere length and yeast cell viability.

Main Methods:

• Examined genetic interactions between CDC73 (PAF1 component) and VPS36.
• Assessed synthetic sickness and lethality between deletions of PAF1 and ESCRT components.
• Quantified RNA levels of VPS36 and other ESCRT components.
• Measured telomere length in different yeast genetic backgrounds (S288C and W303).

Main Results:

• Documented adjacent gene effects between CDC73 and VPS36.
• Observed synthetic sickness between vps36Δ and deletions of PAF1 complex components (cdc73Δ, paf1Δ, ctr9Δ).
• Found synthetic lethality between paf1Δ, ctr9Δ and deletions of other ESCRT complexes (ESCRT-I, -II, -III).
• Demonstrated positive RNA regulation of VPS36 by all PAF1 complex components.
• Showed that ESCRT component deletions shorten telomeres in the S288C background but not W303.

Conclusions:

• Complex genetic interactions exist between PAF1 and ESCRT-II components, both in cis and in trans.
• These interactions influence yeast telomere function and cell viability.
• Gene proximity effects and inter-complex relationships are critical for interpreting yeast genetic data.