Differential stoichiometry among core ribosomal proteins

TL;DR

This study uses mass spectrometry to reveal that core ribosomal protein composition varies with growth conditions and ribosome state, challenging the idea of fixed ribosomal stoichiometry and linking composition to cell fitness.

Contribution

It provides direct quantitative evidence that ribosomal protein composition is variable and functionally relevant, advancing understanding of ribosome heterogeneity.

Findings

Ribosomal protein stoichiometry varies with growth conditions and ribosome state.

Cell fitness correlates with enrichment of specific RPs in polysomes.

Ribosomes exhibit distinct protein compositions with physiological implications.

Abstract

Understanding the regulation and structure of ribosomes is essential to understanding protein synthesis and its deregulation in disease. While ribosomes are believed to have a fixed stoichiometry among their core ribosomal proteins (RPs), some experiments suggest a more variable composition. Testing such variability requires direct and precise quantification of RPs. We used mass-spectrometry to directly quantify RPs across monosomes and polysomes of mouse embryonic stem cells (ESC) and budding yeast. Our data show that the stoichiometry among core RPs in wild-type yeast cells and ESC depends both on the growth conditions and on the number of ribosomes bound per mRNA. Furthermore, we find that the fitness of cells with a deleted RP-gene is inversely proportional to the enrichment of the corresponding RP in polysomes. Together, our findings support the existence of ribosomes with distinct protein composition and physiological function.