Ribosomes are not uniform protein factories. Compelling evidence suggests that variants in composition and structure give rise to distinct populations that finely regulate the translation of specific mRNAs. Variants accommodate different protein needs for different tissues, cell types, environmental conditions, or treatments.
Multiple studies underscore the vital contributions of specialized ribosomes to human health and diseases such as cancer and neurological disorders. For example, ribosomopathies that are specific to particular tissues are characteristic of disorders such as Diamond-Blackfan anemia, isolated congenital asplenia, and Treacher Collins syndrome. These disorders arise from mutations in ribosomal proteins or ribosome biogenesis factors.
The emerging consensus suggests that ribosome heterogeneity is a fundamental mechanism governing post-transcriptional control of gene expression and cellular homeostasis. Ribosomal protein paralogs and rRNA variants are key players in shaping ribosome heterogeneity. However, numerous questions persist regarding the precise functions of distinct ribosome populations and how dysregulation might lead to disease.
Advancements in isolating and studying heterogeneous ribosomes within cells and in cell-free systems are imperative to delve deeper into how specialized ribosomes impact crucial processes such as development, differentiation, drug response, and the cell cycle. Gaining new understanding of dysfunction in ribosome specialization may open a completely new landscape to significantly influence RNA medicine and human health.
The future holds promise for further insights through high-resolution structural studies, innovative techniques, and multidisciplinary research that integrates genomics, proteomics, biochemistry, and cell biology.
Immagina's RiboLace and AHARIBO provide a unique approach to investigating ribosome heterogeneity, providing valuable resources for researchers aiming to unravel the nuances of ribosome specialization and its implications for advancing RNA medicine and human health.
References
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- Jansson, M. D. et al. Regulation of translation by site-specific ribosomal RNA methylation. Nat Struct Mol Biol 28, 889–899 (2021).
- Genuth, N. R. & Barna, M. Ribosome specialization in glioblastoma. Nat Cell Biol 24, 1451–1453 (2022).
- Rothschild, D. et al. Diversity of ribosomes at the level of rRNA variation associated with human health and disease. bioRxiv (2023) doi:10.1101/2023.01.30.526360.
- Genuth, N. R. & Barna, M. Heterogeneity and specialized functions of translation machinery: from genes to organisms. Nat Rev Genet 19, 431–452 (2018).
- Bartsch, D. et al. mRNA translational specialization by RBPMS presets the competence for cardiac commitment in hESCs. Sci Adv 9, (2023).
- Tierney, J. A. S. et al. Ribosome Decision Graphs for the Representation of Eukaryotic RNA Translation Complexity. bioRxiv 2023.11.10.566564 (2023) doi:10.1101/2023.11.10.566564.
- Kampen, K. R., Sulima, S. O., Vereecke, S. & De Keersmaecker, K. Hallmarks of ribosomopathies. Nucleic Acids Res 48, 1013–1028 (2020).