Trends in Genetics
OpinionPimp My Ribosome: Ribosomal Protein Paralogs Specify Translational Control
Section snippets
Defining Ribosome Heterogeneity
The cellular proteome can be highly diversified, especially in higher eukaryotes, to create vastly different cell types and accommodate different functions that can be responsive to the cellular environment. Ribosomes, extraordinarily complex multisubunit molecular machines comprising rRNA and RPs, translate the genetic code into polypeptides 1, 2, 3. While this protein factory has been the subject of intense study for decades, key questions remain regarding its direct role in the control of
RP Paralogs: Sibling Rivalry or Just Doing Their Own Thing?
Chromosome duplication early in eukaryote evolution and continued gene maintenance [13] is one reason why some RPs exist in paralog pairs in both lower and higher eukaryotes. However, for such pairs to have been maintained it has been proposed that individual isoforms might possess functional specificity and confer unique functions independent of their partner paralog (a.k.a. paralog specificity) 4, 7, 8, 9, 10, 14. Clues to the functional benefit of paralog specificity come from diverse
RP Paralog Specificity in Translational Control: New Evidence for Specialized Ribosomes
Numerous reviews have already compiled the wealth of evidence for RP specificity and potential for specialized ribosomes in Escherichia coli, yeast, Dictyostelium, Arabidopsis, zebrafish, and mice 4, 7, 8, 9, 10. In general, studies from the different organisms suggest that many RPs exist in discrete paralog pairs that show at least partial redundancy, in that cells remain viable on the loss or altered expression of one isoform, but since changes in isoform abundance may incur prominent
RAPs and Ribosome Targeting
In addition to canonical RPs that are incorporated into ribosomes during assembly, RAPs may associate with intact ribosomes, subunits, and perhaps specific RPs. Identified in earlier studies, RAPs include Reaper, RACK1/Asc1 (postulated to be a core RP), mTORC2, GYS1, fragile-X mental retardation protein (FMRP), and others. RAP interactions with ribosomes may expand their functional diversity and also allow the translational control of mRNA.
Barna and colleagues [34] performed a ribointeractome
Concluding Remarks: Future Directions and Considerations
The work of Silver and colleagues (2007) was perhaps the first in-depth demonstration that paralogous RPs can be functionally distinct and exhibit specific effects on gene expression [14]. While questions abound regarding the mechanism, the works described here further implicate RP specificity and, perhaps, RAPs in the translational control of subsets of mRNAs in eukaryotes 23, 24, 25, 34. Although it is clear that much more work remains (see Outstanding Questions), the studies presented here
Acknowledgments
Special thanks to Dr Anat Bashan (Department of Structural Biology, Weizmann Institute of Science), who was extremely helpful and generously created the schematic of the 80S ribosome in Figure 3. Thanks also to Drs Gal Haimovich and Nadav Segev for critical reading of the manuscript. J.E.G. holds the Besen-Brender Chair in Microbiology and Parasitology (Weizmann Institute of Science). This study was supported by a grant from the Kahn Center for Systems Biology (Weizmann Institute of Science).
Glossary
- Internal ribosome entry site (IRES)
- sequence element in the 5′UTR of an mRNA that confers translation initiation independent of the 5′ cap.
- Paralog pairs
- pairs of homologous genes that arose from a common ancestral sequence but have diverged within a species to yield proteins that may have different functions.
- Pseudouridylation
- the isomerization of uridine residues in RNA in which uracil is attached to the ribose moiety via a carbon–carbon bond. Pseudouridine incorporation into RNA can confer
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2021, Molecular Aspects of MedicineCitation Excerpt :This hypothesis was challenged after finding that the ribosome composition differs according to the physiological conditions and other variables (Deusser and Wittmann 1972). Ribosome heterogeneity in eukaryotes is attributed to fundamental physiology, development, and diseases (Parenteau et al., 2015; Genuth and Barna 2018a, 2018b; Gerst 2018). The heterogeneity in this context means composition variation in ribosomes because of their rRNA, proteins, or post-transcriptional/translational modifications.