Ribosomal Biogenesis and Heterogeneity in Development, Disease, and Aging

Abstract

Although reported in the literature, ribosome heterogeneity is a phenomenon whose extent and implications in cell and organismal biology is not fully appreciated. This has been the case due to the lack of the appropriate techniques and approaches. Heterogeneity can arise from alternative use and differential content of protein and RNA constituents, as well as from post-transcriptional and post-translational modifications. In the few examples we have, it is apparent that ribosomal heterogeneity offers an additional level and potential for gene expression regulation and might be a way towards tuning metabolism, stress, and growth programs to external and internal stimuli and needs. Here, we introduce ribosome biogenesis and discuss ribosomal heterogeneity in various reported occasions. We conclude that a systematic approach in multiple organisms will be needed to delineate this biological phenomenon and its contributions to growth, aging, and disease. Finally, we discuss ribosome mutations and their roles in disease.

Keywords: aging; disease; growth; protein translation; ribosome biogenesis; ribosomes; stress.

Figure 1

Ribosome biogenesis model in yeast. Transcription of primary 35S rRNA transcript, the common precursor of 18S, 5.8S, and 25S rRNAs, by Pol I from rDNA repeats, together with co-transcriptional joining of U3 snoRNP, r-proteins, and 40S assembly factors, form the 90S ribosomal precursor. 5S rRNA is transcribed separately by Pol III for assembly of 5S RNP before joining the 60S pre-ribosome. Co-transcriptional cleavage of 35S rRNA at the A2 site separates the 60S and 40S r-subunit maturation pathways. Pre-ribosomal particles undergo a cascade of maturation steps in the nucleoplasm by transient association with assembly factors until reaching nuclear export competency. Once exported to the cytoplasm, the last maturation events and quality control steps can occur, resulting in functional r-subunit production. (Adapted from [8] and licensed under the terms of the Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution, and reproduction in any medium or format. We thank Vikram Govind Panse for direct permission to use the figure. No alterations have been introduced from the source.).