PT - JOURNAL ARTICLE AU - Nikolai Slavov AU - Stefan Semrau AU - Edoardo Airoldi AU - Bogdan A. Budnik AU - Alexander van Oudenaarden TI - Variable stoichiometry among core ribosomal proteins AID - 10.1101/005553 DP - 2014 Jan 01 TA - bioRxiv PG - 005553 4099 - http://biorxiv.org/content/early/2014/05/26/005553.short 4100 - http://biorxiv.org/content/early/2014/05/26/005553.full AB - Understanding the regulation and structure of the eukaryotic ribosome is essential to understanding protein synthesis and its deregulation in disease. Traditionally ribosomes are believed to have a fixed stoichiometry among their core ribosomal proteins (RPs), but recent experiments suggest a more variable composition1–6. Reconciling these views requires direct and precise quantification of RPs. We used mass-spectrometry to directly quantify RPs across monosomes and polysomes of budding yeast and mouse embryonic stem cells (ESC). 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 ribosomes bound to multiple mRNAs. Together, these findings support the existence of ribosomes with distinct protein composition and physiological function.