Curr Biol. 2022 Jun 20. pii: S0960-9822(22)00719-9. [Epub ahead of print]32(12):
R611-R617
Cell growth relies upon the ability to produce new proteins, which requires energy and chemical precursors, and an adequate supply of the molecular machines for protein synthesis - ribosomes. Although not widely appreciated, ribosomes are remarkably abundant in all cells. For example, in a rapidly growing yeast cell there are ∼2-4 x 105 ribosomes, produced and exported to the cytoplasm at a rate of ∼2,000-4,000 per minute, with ribosomal proteins making up ∼50% of total cellular protein number and ∼30% of cellular protein mass. Even in a typical human cell ribosomal proteins constitute ∼4-6% of total protein mass, and ribosomes are present at ∼107 per cell. We begin this primer by exploring the tight relationship between ribosome production and cell growth, which has important implications not just for the cell's global protein expression profile and maximum growth rate, but also for the molecular composition of the ribosome itself. We then discuss how and to what extent the expression of the RNA and protein components of ribosomes is fine-tuned to match the cell's needs and minimise waste. Finally, we highlight the importance of coordinated ribosomal RNA (rRNA) and ribosomal protein expression in eukaryotes and explore how defects in this process are associated with proteotoxicity and disease. A central underlying question addressed throughout is whether regulation of ribosome biogenesis has evolved to optimise energy efficiency or is instead (or in addition) driven by other goals, such as maximising cell growth rate, promoting adaptation to changing environmental conditions, or maintaining the stability of the cellular proteome.