Ribosome heterogeneity in development and disease.

Area of Science:

• Molecular Biology
• Cell Biology
• Proteomics

Background:

• The ribosome, traditionally seen as homogeneous, is now recognized for functional specialization.
• Evidence for pervasive ribosome heterogeneity across diverse biological contexts is limited.

Purpose of the Study:

• To investigate the extent and functional relevance of ribosome heterogeneity across various biological states.
• To establish ribosome ratio-omics (RibosomeR) as a tool for analyzing ribosome protein stoichiometry.

Main Methods:

• Utilized existing proteomic data and developed ribosome ratio-omics (RibosomeR) to analyze ribosome protein stoichiometry.
• Applied RibosomeR to diverse samples including different tissues, developmental stages (spermatogenesis), in vitro neuronal maturation, tumors, and immune-challenged macrophages.

Main Results:

• Demonstrated significant ribosome heterogeneity across multiple tissues (fat, spleen, liver, kidney, heart, skeletal muscle).
• Identified distinct RibosomeR signatures during spermatogenesis and dynamic changes during neuronal maturation.
• Linked RibosomeR signatures to tumorigenesis pathways in gastric tumors and dynamic alterations in macrophages after immune challenge.

Conclusions:

• Ribosome heterogeneity is a pervasive cellular phenomenon impacting function, development, and disease.
• RibosomeR is a valuable tool for characterizing ribosome specialization and its biological implications.