Ribosomes and Ribosomal Proteins: More Than Just ‘Housekeeping’

Abstract

Abstract As the catalyst for protein synthesis, the omnipresent ribosome is essential to all organisms. In mammalian cells, the ribosome is composed of four ribosomal ribonucleic acid (RNA) species and 79 different ribosomal proteins . Several hundred copies of the genes encoding the ribosomal RNAs form clusters within the human genome; by contrast, the genes encoding the ribosomal proteins are widely dispersed, although they are functionally related and coordinately expressed. Ribosome biogenesis is a tightly controlled multi‐step process that requires massive cellular energy. Over the past decade, our perception of the ribosome has changed significantly. In the past, ribosomes were considered critical for cellular survival. However, it has now become clear that defects in ribosome biogenesis cause pleiotropic effects that may manifest as specific disease conditions in humans. Ribosomal proteins, which were previously considered to play only a housekeeping role, are now known to have many extraribosomal functions, including the surveillance of ribosomal integrity. Key Concepts: All of the three RNA polymerases, several accessory proteins, and numerous small nucleolar RNAs act in a coordinated manner to ensure that ribosomal RNAs (rRNAs) and ribosomal proteins (RPs) are properly synthesised and assembled into a functionally active ribosome. The numbers of rRNAs and RPs vary between eukaryotes, archaea, and bacteria; however, the functions of ribosomal components have been conserved to a substantial degree throughout evolution. The nucleolus, a sub‐compartment of the nucleus that assembles around the rDNA clusters, is the major site of ribosome production. In general, RPs are basic proteins and exhibit specific affinities for nucleic acids; however, four RPs have acidic pI values. In humans, the genes encoding rRNAs are usually clustered together in multiple copies within the genome; whereas, the genes for the RPs, which are typically encoded by single genes, are scattered through out the genome. Over the past two decades, RPs have been implicated in many cellular activities that are distinct from their primary functions in ribosome biogenesis. The p53 tumour suppressor protein, an important component in the cellular response to a variety of stressors, monitors the fidelity of ribosome biogenesis through a surveillance mechanism that involves several RPs. The disruption of ribosome biogenesis causes ‘nucleolar stress’ that triggers the p53‐signalling pathway, resulting in cell cycle arrest and apoptosis. Haploinsufficiency in RP genes or mutations in genes that encode proteins essential for ribosome biogenesis can lead to a specific class of diseases in humans, called ribosomopathies, which often manifest as prominent tissue‐specific defects with associated pleiotropic anomalies.