Pathways to Specialized Ribosomes: The Brussels Lecture

Abstract

“Specialized ribosomes” is a topic of intense debate and research whose provenance can be traced to the earliest days of molecular biology. Here, the history of this idea is reviewed, and critical literature in which the specialized ribosomes have come to be presently defined is discussed. An argument supporting the evolution of a variety of ribosomes with specialized functions as a consequence of selective pressures acting on a near-infinite set of possible ribosomes is presented, leading to a discussion of how this may also serve as a biological buffering mechanism. The possible relationship between specialized ribosomes and human health are explored. A set of criteria and possible approaches are also presented to help guide the definitive identification of “specialized” ribosomes, and this is followed by a discussion of how synthetic biology approaches might be used to create new types of special ribosomes.

Regulation of mRNA Translation in Neurons—A Matter of Life and Death

“…However, these findings raise additional questions regarding the role for such regulation. Recent studies suggest that heterogeneity in the translational machinery, such as that observed for ribosomal proteins, may influence cell type- or developmental stage-specific translation (reviewed in Dinman, 2016; Xue and Barna, 2012). In addition, growing evidence indicates that many components of the translational machinery, including tRNA synthetases and tRNAs themselves, have a wide range of cellular functions (reviewed in Guo and Schimmel, 2013; Schimmel, 2017).…”

Expression of ribosomopathy genes during Xenopus tropicalis embryogenesis

“…However, an emerging body of research suggests that this is not the case. In particular, the diverse tissue specific phenotypes observed in human ribosomopathies and animal models point to an intriguing variation in requirements for ribosome biogenesis factors and/or ribosome biology during development [1, 4, 6, 7, 16, 25, 32, 36, 42, 46, 47, 50]. Here, we examined the developmental expression patterns of 13 ribosome-associated genes in Xenopus .…”

“…Several ribosome biogenesis factors and proteins have extra-ribosomal functions [16, 19, 44, 48, 61–63], or roles in selective translation of internal ribosome entry site mRNAs [16, 43, 46, 47, 64], which may also contribute to ribosomopathy phenotypes. “Specialized ribosomes”, tailored to preferentially translate specific mRNAs, or to have specific properties in particular environments are another possibility [6, 16, 17, 25, 46, 47, 50]. Support for this is found primarily in observations that ribosomal gene expression levels do vary between tissues [6, 7, 49, 51, 65, 66], and direct evidence of a regulatory role for individual RP proteins in selective mRNA translation and embryonic tissue patterning [6, 16, 43, 49, 50].…”

“…“Specialized ribosomes”, tailored to preferentially translate specific mRNAs, or to have specific properties in particular environments are another possibility [6, 16, 17, 25, 46, 47, 50]. Support for this is found primarily in observations that ribosomal gene expression levels do vary between tissues [6, 7, 49, 51, 65, 66], and direct evidence of a regulatory role for individual RP proteins in selective mRNA translation and embryonic tissue patterning [6, 16, 43, 49, 50]. Furthermore, in Dictyostelium ribosome composition appears to shift with cell cycle [67, 68].…”

An emerging role for the ribosome as a nexus for post-translational modifications

“…Reduction of Rpl38/eL38 in a mouse model revealed that it does not affect global translational regulation but is selectively required for the translation of specific Hox genes that control patterning of the mammalian body plan through cis -regulatory elements residing in their 5′ untranslated regions (UTRs) [9,10•]. Emerging studies that highlight the functional significance of different RPs serving specific roles are reviewed elsewhere [11,12] and they suggest that the ribosome is not merely a static machine, but rather a dynamic one whose intrinsic components can be regulated and diversified to promote intricate regulation of translation.…”