Analyzing Ribosome Remodeling in Health and Disease

Abstract

Increasing evidence suggests that ribosomes actively regulate protein synthesis. However, much of this evidence is indirect, leaving this layer of gene regulation largely unexplored, in part due to methodological limitations. Indeed, evidence is reviewed demonstrating that commonly used methods, such as transcriptomics, are inadequate because the variability in mRNAs coding for ribosomal proteins (RP) does not necessarily correspond to RP variability. Thus protein remodeling of ribosomes should be investigated by methods that allow direct quantification of RPs, ideally of isolated ribosomes. Such methods are reviewed, focusing on mass spectrometry and emphasizing method‐specific biases and approaches to control these biases. It is argued that using multiple complementary methods can help reduce the danger of interpreting reproducible systematic biases as evidence for ribosome remodeling.

The Effect of Interferons on Presentation of Defective Ribosomal Products as HLA Peptides

“…IFNs regulate the expression and activities of different proteins by altering posttranslational modifications ( 23 , 93 ) and by synthesis or degradation of specific subunits ( 31 ). Identification of alterations in the subunit compositions of protein complexes was followed through isolation of protein complexes or full-proteome analyses while looking for deviations from the stoichiometry of these subunits ( 76 , 77 , 94 ). However, following the degradation schemes of the surplus subunits before they are incorporated into the protein complexes is very challenging because the degradation process is often too rapid to be followed through proteolysis intermediates.…”

“…While the effects of IFNs on ribosome subunits have been less studied, the interactions of both 40S and 60S ribosomal proteins with viruses have been studied extensively and determined to be important in the translation of viral components needed for the assembly of new virions ( 97 , 98 , 99 , 100 , 101 , 102 ). Modulation of ribosomal protein synthesis and assembly in response to viral infection ( 77 , 94 ) provides a mechanism for preventing the assembly of the 80S ribosome, which subsequently curbs the synthesis of viral proteins. Another possibility is that during viral infection, cells produce special types of ribosomes, called immunoribosomes, with different subunit compositions ( 103 , 104 ).…”

BRIX1 Promotes Ribosome Synthesis and Enhances Glycolysis by Selected Translation of GLUT1 in Colorectal Cancer

“…Finally, mature ribosomal executive protein translation function is formed(4). Among them, rDNA transcription to form rRNA is crucial, which directly determines the rate of ribosome synthesis (19,20). The transcriptional process of rRNA involves the activation of RNA polymerase Pol I/III, UBF recruitment, non-coding RNAs, regulation of nucleolins and ribosomal-related proteins, and splicing and processing of precursor RNAs, forming a complex molecular regulatory network, among which the interactions between related molecules are particularly important (20,21).…”

Scaling Up Single-Cell Proteomics

“…Such community standards are urgently needed to support the wider adoption and scaling up of single-cell proteomics. Specifically, these metrics must distinguish between reproducibility and quantitative accuracy, between accuracy of relative and absolute quantification, between the variety of approaches used for computing coefficients of variation, and many other quantitative measurements that are currently conflated in single-cell MS publications ( 18 , 49 , 50 ). These community standards should reflect a broad consensus, and indeed conference workshops have begun discussions toward formulating such standards ( http://workshop2019.single-cell.net/ ).…”