Integrating Rio1 activities discloses its nutrient-activated network in Saccharomyces cerevisiae

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Saccharomyces cerevisiae Rio1 regulates crucial cellular processes including transcription, RNA processing, and ribosome biogenesis.
• Its human ortholog, RIOK1, is implicated in tumor growth and metastasis, highlighting potential conserved roles in disease.
• The global functions of Rio1 and its regulatory network remain largely uncharacterized.

Purpose of the Study:

• To elucidate the comprehensive signaling network governed by Rio1 in Saccharomyces cerevisiae.
• To identify the direct and indirect targets and functions of Rio1 at the protein, chromatin, and RNA levels.
• To explore the conserved functions of Rio1 and its potential implications in human diseases like cancer.

Main Methods:

• Systematic identification of Rio1 physical interactors.
• Global profiling of Rio1 target genes and transcripts.
• Chromatin immunoprecipitation sequencing (ChIP-seq) to map Rio1-binding sites.
• Integration of experimental data with existing yeast interaction databases using network computation.
• Experimental validation of network components and subcellular localization studies.

Main Results:

• Rio1 directly and indirectly manages an essential signaling network affecting protein, chromatin, and RNA.
• Rio1 orchestrates cell growth and division in response to nutrient availability, parallel to the Tor1 kinase pathway.
• The Rio1 network regulates protein synthesis, ribosome biogenesis and activity, protein turnover via the 26S proteasome, and impacts metabolic and cell-cycle programs.
• Rio1 was localized to mitochondria and vacuoles, indicating broader cellular roles.
• Rio1 activity and network functions are conserved in humans.

Conclusions:

• Rio1 is a central regulator of fundamental cellular processes, including growth, division, and homeostasis, through a complex signaling network.
• The conserved nature of Rio1 suggests its dysregulation in human cells, particularly RIOK1 in cancer, may drive pathological processes like uncontrolled proliferation and metabolic reprogramming.
• This study provides a foundation for understanding the multifaceted roles of Rio1 and its implications in both normal physiology and disease.