Ribosome-associated proteins: unwRAPping ribosome heterogeneity in the twenty-first century.

The definition of the ribosome as the monolithic machinery in cells that synthesizes all proteins in the cell has persisted for the better part of a century. Yet, research has increasingly revealed that ribosomes are dynamic, multimodal complexes capable of fine-tuning gene expression. This translation regulation may be achieved by ribosome-associated proteins (RAPs), which play key roles as modular trans-acting factors that are dynamic across different cellular contexts and can mediate the recruitment of specific transcripts or the modification of RNA or ribosomal proteins. As a result, RAPs have the potential to rapidly regulate translation within specific subcellular regions, across different cell or tissue types, in response to signalling, or in disease states. In this article, we probe the definition of the eukaryotic ribosome and review the major layers of additional proteins that expand the definition of ribosomes in the twenty-first century. We pose RAPs as key modulators that impart ribosome function in cellular processes, development and disease.This article is part of the discussion meeting issue 'Ribosome diversity and its impact on protein synthesis, development and disease'.