The Modular Adaptive Ribosome

Yadav, A. S.; Radhakrishnan, Aparna; Panda, Anshuman; Singh, Amartya; Sinha, Himanshu; Bhanot, Gyan

doi:10.1371/journal.pone.0166021

Cited by 12 publications

(16 citation statements)

References 60 publications

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“…These data show that the defects which appear to be paralog-specific come instead from differences in paralog expression that originate in the mRNA UTRs, their promoter regions, or both. Importantly, paralog mRNA levels do not always react similarly to cellular perturbations (Gasch et al 2000;Yadav et al 2016). For example, most RP paralogs are similarly regulated during stress, but the Rpl13 and Rpl18 paralogs diverge during cell quiescence, and the expression of 5 paralogs is decoupled during the response to heat shock (Fig.…”

Section: The Expression Of Ribosomal Protein Paralogs Is Differentialmentioning

confidence: 99%

Does functional specialization of ribosomes really exist?

Ferretti

Karbstein

2019

RNA

109

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It has recently become clear that ribosomes are much more heterogeneous than previously thought, with diversity arising from rRNA sequence and modifications, ribosomal protein (RP) content and posttranslational modifications (PTMs), as well as bound nonribosomal proteins. In some cases, the existence of these diverse ribosome populations has been verified by biochemical or structural methods. Furthermore, knockout or knockdown of RPs can diversify ribosome populations, while also affecting the translation of some mRNAs (but not others) with biological consequences. However, the effects on translation arising from depletion of diverse proteins can be highly similar, suggesting that there may be a more general defect in ribosome function or stability, perhaps arising from reduced ribosome numbers. Consistently, overall reduced ribosome numbers can differentially affect subclasses of mRNAs, necessitating controls for specificity. Moreover, in order to study the functional consequences of ribosome diversity, perturbations including affinity tags and knockouts are introduced, which can also affect the outcome of the experiment. Here we review the available literature to carefully evaluate whether the published data support functional diversification, defined as diverse ribosome populations differentially affecting translation of distinct mRNA (classes). Based on these observations and the commonly observed cellular responses to perturbations in the system, we suggest a set of important controls to validate functional diversity, which should include gainof-function assays and the demonstration of inducibility under physiological conditions.

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Section: The Expression Of Ribosomal Protein Paralogs Is Differentialmentioning

confidence: 99%

Does functional specialization of ribosomes really exist?

Ferretti

Karbstein

2019

RNA

109

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“…These studies recently culminated with the assessment of ribosomal heterogeneity across a hundred cell types and tissues in mouse and human (Yadav et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Expression of distinct maternal and somatic 5.8S, 18S, and 28S rRNA types during zebrafish development

Locati

Pagano

Girard

et al. 2017

RNA

127

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There is mounting evidence that the ribosome is not a static translation machinery, but a cell-specific, adaptive system. Ribosomal variations have mostly been studied at the protein level, even though the essential transcriptional functions are primarily performed by rRNAs. At the RNA level, oocyte-specific 5S rRNAs are long known for Xenopus. Recently, we described for zebrafish a similar system in which the sole maternal-type 5S rRNA present in eggs is replaced completely during embryonic development by a somatic-type. Here, we report the discovery of an analogous system for the 45S rDNA elements: 5.8S, 18S, and 28S. The maternal-type 5.8S, 18S, and 28S rRNA sequences differ substantially from those of the somatic-type, plus the maternal-type rRNAs are also replaced by the somatic-type rRNAs during embryogenesis. We discuss the structural and functional implications of the observed sequence differences with respect to the translational functions of the 5.8S, 18S, and 28S rRNA elements. Finally, in silico evidence suggests that expansion segments (ES) in 18S rRNA, previously implicated in ribosome-mRNA interaction, may have a preference for interacting with specific mRNA genes. Taken together, our findings indicate that two distinct types of ribosomes exist in zebrafish during development, each likely conducting the translation machinery in a unique way.

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“…Proteomic and transcriptomic analyses found evidence for the existence of ribosomal subpopulations which differed in composition, interactomes, and perhaps mRNA specificity (Yadav et al, 2016;Shi et al, 2017;Segev and Gerst, 2018).…”

Section: Introductionmentioning

confidence: 99%

Regulation of yeast RPL22B splicing depends on intact pre-mRNA context of the intron

Abrhámová

Folk

2019

Preprint

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Yeast RPL22A and RPL22B genes form an intergenic regulatory loop modulating the ratio of paralogous transcripts in response to changing levels of proteins. Gabunilas and Chanfreau (Gabunilas and Chanfreau, PLoS Genet 12, e1005999, 2016) and our group (Abrhámová et al., PLoS ONE 13, e0190685, 2018) described that Rpl22 proteins bound to the divergent introns of RPL22 paralogs and inhibited splicing in dosage dependent manner.Here, we continued to study the splicing regulation in more detail and designed constructs for in vivo analyses of splicing efficiency. We also tested Rpl22 binding to RPL22B intron in three-hybrid system. We were able to confirm the findings reported originally by Gabunilas and Chanfreau on the importance of a stem loop structure within the RPL22B intron.Mutations which lowered the stability of the structure abolished Rpl22-mediated inhibition. In contrast, we were not able to confirm the sequence specificity with respect to either Rpl22 binding or splicing inhibition within this region, which they reported. We contradict their results that the 'RNA internal loop' of RPL22Bi (nt 178CCCU181 and 221UGAA224) is crucial for mediating the Rpl22 effects. We assume that this discrepancy reflects the difference in constructs, as the reporters used by Gabunilas and Chanfreau lacked the alternative 5' splice site as well as surrounding exons. Our own comparison confirms that deleting the sequence spanning alternative 5' splice site lowers splicing efficiency, hinting to possible disturbances of the regulatory mechanism. We argue that the structural context of the 'regulatory element' may reach across the intron or into the surrounding sequences, similarly to what was found previously for other genes, such as RPL30. Apparently, more detailed analyses are needed to discern this intriguing example of splicing regulation.

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The Modular Adaptive Ribosome

Cited by 12 publications

References 60 publications

Does functional specialization of ribosomes really exist?

Does functional specialization of ribosomes really exist?

Expression of distinct maternal and somatic 5.8S, 18S, and 28S rRNA types during zebrafish development

Regulation of yeast RPL22B splicing depends on intact pre-mRNA context of the intron

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