Specialized ribosomes and specific ribosomal protein paralogs control translation of mitochondrial proteins

Segev, Nadav; Gerst, Jeffrey E.

doi:10.1083/jcb.201706059

Cited by 90 publications

(98 citation statements)

References 59 publications

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“…Notably, two other RPs with highly similar paralogues, uL2b and eS26b (Rpl2b and Rps26b), show the same phenotype (Segev & Gerst, ). The uL1 mutant strains translate different mRNAs, as shown by PUNCH‐P (Aviner, Geiger, & Elroy‐Stein, ), with the uL1b deletion strain failing to efficiently translate mitochondrial and cell wall‐related proteins (Segev & Gerst, ). It remains unclear how uL1a‐ and uL1b‐containing ribosomes could differ in their translational activity, but it is again possible that non‐coding sequences could have an influence, perhaps via directing differential processing of the two mRNAs.…”

Section: Mrna‐specific Regulation: Ribosomal Specialization and Transmentioning

confidence: 99%

“…Notably, two other RPs with highly similar paralogues, uL2b and eS26b (Rpl2b and Rps26b), show the same phenotype (Segev & Gerst, 2018). The uL1 mutant strains translate different mRNAs, as shown by PUNCH-P (Aviner, Geiger, & Elroy-Stein, 2013), with the uL1b deletion strain failing to efficiently translate mitochondrial and cell wall-related proteins (Segev & Gerst, 2018).…”

Section: Paralogue-specific Differences In Rp Functionmentioning

confidence: 99%

“…The RP paralogue pair uL1a and uL1b (Rpl1a and Rpl1b) are absolutely identical, but individual deletion mutants of the two also exhibit phenotypic differences. uL1b, but not uL1a, mutant strains are respiratory deficient, showing slow growth on fermentable carbon sources and none on non‐fermentable carbon sources (Segev & Gerst, ). Notably, two other RPs with highly similar paralogues, uL2b and eS26b (Rpl2b and Rps26b), show the same phenotype (Segev & Gerst, ).…”

Section: Mrna‐specific Regulation: Ribosomal Specialization and Transmentioning

confidence: 99%

“…uL1b, but not uL1a, mutant strains are respiratory deficient, showing slow growth on fermentable carbon sources and none on non‐fermentable carbon sources (Segev & Gerst, ). Notably, two other RPs with highly similar paralogues, uL2b and eS26b (Rpl2b and Rps26b), show the same phenotype (Segev & Gerst, ). The uL1 mutant strains translate different mRNAs, as shown by PUNCH‐P (Aviner, Geiger, & Elroy‐Stein, ), with the uL1b deletion strain failing to efficiently translate mitochondrial and cell wall‐related proteins (Segev & Gerst, ).…”

Section: Mrna‐specific Regulation: Ribosomal Specialization and Transmentioning

confidence: 99%

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Translational regulation in response to stress in Saccharomyces cerevisiae

Crawford

Pavitt

2018

Yeast

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The budding yeast Saccharomyces cerevisiae must dynamically alter the composition of its proteome in order to respond to diverse stresses. The reprogramming of gene expression during stress typically involves initial global repression of protein synthesis, accompanied by the activation of stress-responsive mRNAs through both translational and transcriptional responses. The ability of specific mRNAs to counter the global translational repression is therefore crucial to the overall response to stress. Here we summarize the major repressive mechanisms and discuss mechanisms of translational activation in response to different stresses in S. cerevisiae. Taken together, a wide range of studies indicate that multiple elements act in concert to bring about appropriate translational responses. These include regulatory elements within mRNAs, altered mRNA interactions with RNA-binding proteins and the specialization of ribosomes that each contribute towards regulating protein expression to suit the changing environmental conditions.

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Section: Mrna‐specific Regulation: Ribosomal Specialization and Transmentioning

confidence: 99%

Section: Paralogue-specific Differences In Rp Functionmentioning

confidence: 99%

Section: Mrna‐specific Regulation: Ribosomal Specialization and Transmentioning

confidence: 99%

Section: Mrna‐specific Regulation: Ribosomal Specialization and Transmentioning

confidence: 99%

See 2 more Smart Citations

Translational regulation in response to stress in Saccharomyces cerevisiae

Crawford

Pavitt

2018

Yeast

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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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BRIX1 promotes ribosome synthesis and enhances glycolysis by selected translation of GLUT1 in colorectal cancer

Jiang,

Sun,

Wen

et al. 2024

The Journal of Gene Medicine

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BackgroundRibosome biogenesis protein BRX1 homolog (BRIX1) is critically required for the synthesis of the 60S ribosome subunit. However, the role and mechanism of BRIX1 in colorectal cancer (CRC) remain unclear.MethodsKyoto Encyclopedia of Gene and Genome pathway and Gene Ontology analyses were used for bioinformatics analysis. The rRNA levels were detected in CRC tissues and cells. Nascent RNA synthesis was detected via cellular immunofluorescence. The correlation was analyzed between patient Positron Emission Tomography‐Computed Tomography (PET–CT) values and their BRIX1 expression. The extracellular acidification rate (ECAR) and oxygen consumption rate were determined via live metabolic analyses. Polysome fractions were collected for BRIX1 mRNA used in translation. The orthotopic model and Cell Counting Kit‐8 (CCK8) assay were used to assess BRIX1 function in CRC.ResultsBRIX1 is a core protein involved in ribosome‐related pathway changes in CRC. Gene Ontology analysis showed that BRIX1 was primarily enriched in ribosome assembly and ribosome biogenesis pathways. In fresh CRC tissue, rRNA levels (5S, 5.8S, 18S and 28S) were higher in the BRIX1 high‐expression group than in the BRIX1 low‐expression group. Similarly, BRIX1 knockdown significantly decreased rRNA levels for 5S, 5.8S, 18S and 28S in CRC cells, whereas overexpression of BRIX1 significantly increased these levels. In addition, BRIX1 knockdown inhibited nascent RNA synthesis in CRC cells. In clinical data analysis, BRIX1 expression was related to the glucose uptake in PET–CT. BRIX1 knockdown significantly decreased the ECAR value, glucose uptake and lactic acid production in CRC cells, whereas BRIX1 overexpression significantly increased these. Furthermore, BRIX1 knockdown significantly decreased the protein expression of GLUT1, whereas BRIX1 overexpression significantly increased this; however, expression of BRIX1 mRNA was unaffected in either case. Blocking glycolysis by si‐GLUT1 or galactose reversed BRIX1 promotion of glycolysis and cell proliferation in CRC cells.

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Specialized ribosomes and specific ribosomal protein paralogs control translation of mitochondrial proteins

Abstract: Ribosomal proteins exist mainly as paralog pairs in eukaryotes, yet the reasons for maintaining duplication are unclear. By using a novel proteomic approach, Segev and Gerst show paralog-specific regulation of the translation of mitochondrial proteins using specialized ribosomes.

Cited by 90 publications

References 59 publications

Translational regulation in response to stress in Saccharomyces cerevisiae

Translational regulation in response to stress in Saccharomyces cerevisiae

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

BRIX1 promotes ribosome synthesis and enhances glycolysis by selected translation of GLUT1 in colorectal cancer

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