Precise Post-translational Tuning Occurs for Most Protein Complex Components during Meiosis

Abstract

SUMMARY Protein degradation is known to be a key component of expression regulation for individual genes, but its global impact on gene expression has been difficult to determine. We analyzed a parallel gene expression dataset of yeast meiotic differentiation, identifying instances of coordinated protein-level decreases to identify new cases of regulated meiotic protein degradation, including of ribosomes and targets of the meiosis-specific anaphase-promoting complex adaptor Ama1. Comparison of protein and translation measurements over time also revealed that, although meiotic cells are capable of synthesizing protein complex members at precisely matched levels, they typically do not. Instead, the members of most protein complexes are synthesized imprecisely, but their protein levels are matched, indicating that wild-type eukaryotic cells routinely use post-translational adjustment of protein complex partner levels to achieve proper stoichiometry. Outlier cases, in which specific complex components show divergent protein-level trends, suggest timed regulation of these complexes.

Proteome Turnover in the Spotlight: Approaches, Applications, and Perspectives

“…Complex turnover is not entirely coherent, but typically sub-clustered based on the architecture of multimeric complexes, with more dynamic subunits showing higher turnover than stabilizing "core" subunits, such as has been seen for the proteasome (50,61,65,123) ( Figure 3B). Additional mechanistic studies have revealed that for some complexes, certain subunits may be translated in excess, then degraded down to stoichiometric equivalencies (29,123). The fact that members of large, multimembered protein complexes are more likely to have different turnover rates depending on subcellular location (54,62) implies that these excesses of protein complex subunits may be generated to favor complex formation in one location distinct from the location where the complex functions (54).…”

“…Another example of a multi-omics approach is from Eisenberg et al (2018), who used matched RNA-sequencing, ribosome profiling, and TMT-based proteomics to look at the temporal changes in gene expression during yeast meiosis (123). Here, ribosome…”

Exploring the Complexity of Protein-Level Dosage Compensation that Fine-Tunes Stoichiometry of Multiprotein Complexes

“…Therefore, NATs-mediated proteolysis seems to be predominantly triggered upon genetic perturbations. It should be noted that because post-translational dosage compensation is widely used to achieve proper stoichiometry in unperturbed yeast cells [ 44 ], physiologically induced stoichiometric imbalance is also fine-tuned by the compensation.…”

Analyzing Ribosome Remodeling in Health and Disease

“…While suggestive evidence for ribosome remodeling has originated from indirect methods (such as measuring transcripts coding for RPs [50,51] ), such data remain inconclusive because RP synthesis and degradation are extensively regulated. [48,49,52,53] RP molecules that are not incorporated into a complex are rapidly degraded. [52] Because of this post-transcriptional regulation, analysis of ribosome remodeling in health and disease should rely on direct protein measurements.…”