Illuminating ribosome biogenesis disorders through structural biology

Ribosomes are essential nanomachines responsible for synthesizing all cellular proteins. Their production, known as ribosome biogenesis, is a highly complex and energy-intensive process that requires the coordinated action of hundreds of proteins and RNA-based trans-acting factors to assemble and mature the functional ribosomal components. Ribosome biogenesis is increasingly recognized as a key contributor to human disease: excessive ribosome production can fuel tumorigenesis, while insufficient or defective ribosome production is observed in a group of tissue-specific disorders known as ribosomopathies. Although the basis of this tissue specificity remains poorly understood, the most commonly affected systems are the blood, brain, and bones. Recent advances in structural biology have yielded high-resolution snapshots of precursor (pre-)ribosomes at various stages of maturation, offering new insights into how pathogenic variants of ribosomal proteins or assembly factors disrupt critical molecular interactions. In this review, we highlight selected examples where structural information is beginning to illuminate the molecular basis of ribosomopathies.