Duplicated ribosomal protein paralogs promote alternative translation and drug resistance

Ghulam, Mustafa Malik; Catala, Mathieu; Reulet, Gaspard; Scott, Michelle S.; Elela, Sherif Abou

doi:10.1038/s41467-022-32717-y

Cited by 11 publications

(10 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well established that the composition of paralogous r-proteins in individual ribosomes often varies in response to developmental or other external stimuli, thereby potentially generating “specialized ribosomes” with altered translational properties. However, a consensus on the biological significance of ribosome heterogeneity has not yet emerged ( 37 – 48 ).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Ribosome Assembly and Ribosome Translation Has Distinctly Different Effects on Abundance and Paralogue Composition of Ribosomal Protein mRNAs in Saccharomyces cerevisiae

et al. 2023

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of Ribosome Assembly and Ribosome Translation Has Distinctly Different Effects on Abundance and Paralogue Composition of Ribosomal Protein mRNAs in Saccharomyces cerevisiae

et al. 2023

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibiting ribosome assembly and ribosome translation have distinctly different effects on the abundance and paralogue composition of ribosomal protein mRNAs inSaccharomyces cerevisiae

Shamsuzzaman

Rahman

Bommakanti

et al. 2022

Preprint

View full text Add to dashboard Cite

Many mutations in genes for ribosomal proteins and assembly factors cause cell stress and altered cell fate resulting in congenital diseases, collectively called ribosomopathies. Even though all such mutations depress the cell's protein synthesis capacity, they generate many different phenotypes, suggesting that the diseases are not due simply to insufficient protein synthesis capacity. To learn more, we have investigated how the global transcriptome in Saccharomyces cerevisiae responds to reduced protein synthesis generated in two different ways: abolishing the assembly of new ribosomes or inhibiting ribosomal function. Our results show that the mechanism by which protein synthesis is obstructed affects the ribosomal protein transcriptome differentially: ribosomal protein mRNA abundance increases during the abolition of ribosome formation but decreases during the inhibition of ribosome function. Interestingly, the ratio between mRNAs from some, but not all, paralogous genes encoding slightly different versions of a given r-protein change differently during the two types of stress, suggesting that specific ribosomal protein paralogues may contribute to the stress response. Unexpectedly, the abundance of transcripts for ribosome assembly factors and translation factors remains relatively unaffected by the stresses. On the other hand, the state of the translation apparatus does affect cell physiology: mRNA levels for some other proteins not directly related to the translation apparatus also change differentially, though not coordinately with the r-protein genes, in response to the stresses.

show abstract

“…Each of these genes has a paralog, as most ribosomal genes in S. pombe do, and is therefore likely somewhat dispensable. Ribosomal paralogs are tuned to certain translational responses in S. cerevisiae (103)(104)(105) . In S. pombe , there is also evidence for paralog-dependent differences in ribosome compositions (106) .…”

Section: Ribosomal Genes and Mlp Formation: A Novel Pathway?mentioning

confidence: 99%

Genetic and environmental determinants of multicellular-like phenotypes in fission yeast

Kӧvér,

Cohen,

Ralser

et al. 2023

Preprint

View full text Add to dashboard Cite

Multicellular fungi have repeatedly given rise to primarily unicellular yeast species. Some of these, includingSchizosaccharomyces pombe, are able to revert to multicellular-like phenotypes (MLP). Our bioinformatic analysis of existing data suggested that, besides some regulatory proteins, most proteins involved in MLP formation are not functionally conserved betweenS. pombeand budding yeast. We developed high-throughput assays for two types of MLP inS. pombe: flocculation and surface adhesion, which correlated in minimal medium, suggesting a common mechanism. Using a library of 57 naturalS. pombeisolates, we found MLP formation to widely vary across different nutrient and drug conditions. Next, in a segregantS. pombelibrary generated from an adhesive natural isolate and the standard laboratory strain, MLP formation correlated with expression levels of the transcription-factor genembx2and several flocculins. Quantitative trait locus mapping of MLP formation located a causal frameshift mutation in thesrb11gene encoding cyclin C, a part of the Cdk8 kinase module (CKM) of the Mediator complex. Other CKM deletions also resulted in MLP formation, consistently through upregulation ofmbx2, and only in minimal media. We screened a library of 3721 gene-deletion strains, uncovering additional genes involved in surface adhesion on minimal media. We identified 31 high-confidence hits, including 19 genes that have not been associated with MLPs in fission or budding yeast. Notably, deletion ofsrb11, unlike deletions of the 31 hits, did not compromise cell growth, which might explain its natural occurrence as a QTL for MLP formation.

show abstract

Duplicated ribosomal protein paralogs promote alternative translation and drug resistance

Cited by 11 publications

References 48 publications

Inhibition of Ribosome Assembly and Ribosome Translation Has Distinctly Different Effects on Abundance and Paralogue Composition of Ribosomal Protein mRNAs in Saccharomyces cerevisiae

Inhibition of Ribosome Assembly and Ribosome Translation Has Distinctly Different Effects on Abundance and Paralogue Composition of Ribosomal Protein mRNAs in Saccharomyces cerevisiae

Inhibiting ribosome assembly and ribosome translation have distinctly different effects on the abundance and paralogue composition of ribosomal protein mRNAs inSaccharomyces cerevisiae

Genetic and environmental determinants of multicellular-like phenotypes in fission yeast

Contact Info

Product

Resources

About