Synergistic effects of TOR and proteasome pathways on the yeast transcriptome and cell growth

Area of Science:

• Cellular Biology
• Molecular Biology
• Yeast Genetics

Background:

• The proteasome's role in gene transcription is known, but its regulation of genome-wide transcription concerning nutrient signaling is unclear.
• Nutrient signaling pathways, like the Target of Rapamycin Complex 1 (TORC1), are crucial for cellular growth and stress responses.

Purpose of the Study:

• To investigate the synergistic regulation of genome-wide transcription by the proteasome and TORC1 signaling.
• To elucidate the molecular mechanisms by which these pathways coordinate cell growth and starvation responses.

Main Methods:

• Utilized chemical inhibitors to impair proteasome and/or TORC1 functions.
• Performed genetic analysis involving key kinases (Yak1, Rim15) and transcription factors (Msn2/4, Gis1).
• Assessed gene expression related to biosynthesis, proteolysis, starvation, and stress responses.

Main Results:

• Proteasome and TORC1 synergistically enhance expression of purine/amino acid biosynthesis genes and repress proteolysis/stress genes.
• TORC1 negatively regulates Yak1 and Rim15 kinases, modulating starvation gene expression via Msn2/4 and Gis1.
• Proteasome inhibition triggers starvation gene transcription and disrupts kinase control, indicating its role in stringent TOR pathway regulation.
• Proteasome and TORC1 synergy impacts cell growth control; Rpn4-dependent proteasome upregulation is vital for responding to reduced TORC1 activity.

Conclusions:

• The proteasome and TOR signaling pathway act synergistically to regulate a substantial portion of the yeast genome.
• This coordinated regulation is essential for balancing cell growth and starvation responses.
• The proteasome ensures stringent control of the starvation response pathway mediated by TOR.