Lso2 is a conserved ribosome-bound protein required for translational recovery in yeast

Wang, Yinuo J.; Vaidyanathan, Pavanapuresan P.; Rojas-Durán, María F.; Udeshi, Namrata D.; Bartoli, Kristen M.; Carr, Steven A.; Gilbert, Wendy V.

doi:10.1371/journal.pbio.2005903

Cited by 40 publications

(70 citation statements)

References 114 publications

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“…In this work, we present Lso2 and CCDC124 in yeast and human cells as new eukaryotic-specific ribosome hibernation factors that play an active role in translation recovery (Wang et al, 2018). Our cryo-EM structures show, that Lso2 and CCDC124 occupy the binding sites of mRNA and tRNA, thereby resembling the mode of action of known bacterial hibernation factors.…”

Section: Discussionmentioning

confidence: 83%

“…In our structure, these contact sites are blocked by Lso2. RNA crosslinking (ePAR-CLIP) data suggested direct interaction of Lso2 with H43/H44 of the GAC (Wang et al, 2018). This interaction is most likely established by the ultimate C-terminus of Lso2, which is not resolved in our maps due to a high degree of flexibility.…”

Section: Lso2 Interacts With Ribosomal Trna and Mrna Binding Sitesmentioning

confidence: 81%

“…Since Lso2 is conserved in higher eukaryotes (Wang et al, 2018), we expanded our studies on its role as a starvation factor in the human system. To that end, human 80S ribosomes were prepared from a HEK293T culture with high cell density.…”

Section: Two Distinct Inactive Ribosomal Species Are Present Eukaryotesmentioning

confidence: 99%

“…Several types of inactive or hibernating ribosomes have also been observed in eukaryotes (Brown et al, 2018;Krokowski et al, 2011). In general, idle 80S ribosomes accumulate after exposure to various stresses like amino acid shortage (Krokowski et al, 2011;Tzamarias et al, in proximity to tRNA, and to rRNA helices H43 and H44 based on chemical crosslinking studies (Wang et al, 2018). This interaction between Lso2 and ribosomes apparently facilitates reactivation of translation upon nutrient upshift and exit from stationary phase.…”

Section: Introductionmentioning

confidence: 99%

“…Ribosomes from lso2Δ show additional functional defects including altered sensitivity to RNase I and altered A site accommodation, as determined by increased incidence of pausing at start codons and enrichment of 21mers in ribosomal profiling -indicative of empty A sites (Wang et al, 2018;Wu et al, 2019). The mode of ribosome interaction and thus the molecular basis for these effects of Lso2 are not understood.…”

Section: Introductionmentioning

confidence: 99%

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Structure and function of yeast Lso2 and human CCDC124 bound to hibernating ribosomes

Wells

Buschauer

Mackens-Kiani

et al. 2020

Preprint

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150)Cells adjust to nutrient deprivation by reversible translational shut down. This is accompanied by maintaining inactive ribosomes in a hibernation state, where they are bound by proteins with inhibitory and protective functions. In eukaryotes, such a function was attributed to Stm1 (SERBP1 in mammals), and recently Lso2 (CCDC124 in mammals) was found to be involved in translational recovery after starvation from stationary phase. Here, we present cryo-electron microscopy (cryo-EM) structures of translationally inactive yeast and human ribosomes. We found Lso2/CCDC124 accumulating on idle ribosomes in the non-unrotated state, in contrast to Stm1/SERBP1-bound ribosomes, which display a rotated state. Lso2/CCDC124 bridges the decoding sites of the small with the GTPase-activating center of the large subunit. This position allows accommodation of the Dom34-dependent ribosome recycling system, which splits Lso2-containing but not Stm1-containing ribosomes. We propose a model in which Lso2 facilitates rapid translation reactivation by stabilizing the recycling-competent state of inactive ribosomes.

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Section: Discussionmentioning

confidence: 83%

Section: Lso2 Interacts With Ribosomal Trna and Mrna Binding Sitesmentioning

confidence: 81%

Section: Two Distinct Inactive Ribosomal Species Are Present Eukaryotesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Structure and function of yeast Lso2 and human CCDC124 bound to hibernating ribosomes

Wells

Buschauer

Mackens-Kiani

et al. 2020

Preprint

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Ribosomal dormancy at the nexus of ribosome homeostasis and protein synthesis

Koli,

Shetty

2024

BioEssays

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Dormancy or hibernation is a non‐proliferative state of cells with low metabolic activity and gene expression. Dormant cells sequester ribosomes in a translationally inactive state, called dormant/hibernating ribosomes. These dormant ribosomes are important for the preservation of ribosomes and translation shut‐off. While recent studies attempted to elucidate their modes of formation, the regulation and roles of the diverse dormant ribosomal populations are still largely understudied. The mechanistic details of the formation of dormant ribosomes in stress and especially their disassembly during recovery remain elusive. In this review, we discuss the roles of dormant ribosomes and their potential regulatory mechanisms. Furthermore, we highlight the paradigms that need to be answered in the field of ribosomal dormancy.

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Dimerization underlies the aggregation propensity of intrinsically disordered coiled‐coil domain‐containing 124

Öztürk

Güllülü

2021

Proteins

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Coiled‐coil domain‐containing 124 (CCDC124) is a recently discovered ribosome‐binding protein conserved in eukaryotes. CCDC124 has regulatory functions on the mediation of reversible ribosomal hibernation and translational recovery by direct attachment to large subunit ribosomal protein uL5, 25S rRNA backbone, and tRNA‐binding P/A‐site major groove. Moreover, it independently mediates cell division and cellular stress response by facilitating cytokinetic abscission and disulfide stress‐dependent transcriptional regulation, respectively. However, the structural characterization and intracellular physiological status of CCDC124 remain unknown. In this study, we employed advanced in silico protein modeling and characterization tools to generate a native‐like tertiary structure of CCDC124 and examine the disorder, low sequence complexity, and aggregation propensities, as well as high‐order dimeric/oligomeric states. Subsequently, dimerization of CCDC124 was investigated with co‐immunoprecipitation (CO‐IP) analysis, immunostaining, and a recent live‐cell protein–protein interaction method, bimolecular fluorescence complementation (BiFC). Results revealed CCDC124 as a highly disordered protein consisting of low complexity regions at the N‐terminus and an aggregation sequence (151‐IAVLSV‐156) located in the middle region. Molecular docking and post‐docking binding free energy analyses highlighted a potential involvement of V153 residue on the generation of high‐order dimeric/oligomeric structures. Co‐IP, immunostaining, and BiFC analyses were used to further confirm the dimeric state of CCDC124 predominantly localized at the cytoplasm. In conclusion, our findings revealed in silico structural characterization and in vivo subcellular physiological state of CCDC124, suggesting low‐complexity regions located at the N‐terminus of disordered CCDC124 may regulate the formation of aggregates or high‐order dimeric/oligomeric states.

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Lso2 is a conserved ribosome-bound protein required for translational recovery in yeast

Cited by 40 publications

References 114 publications

Structure and function of yeast Lso2 and human CCDC124 bound to hibernating ribosomes

Structure and function of yeast Lso2 and human CCDC124 bound to hibernating ribosomes

Ribosomal dormancy at the nexus of ribosome homeostasis and protein synthesis

Dimerization underlies the aggregation propensity of intrinsically disordered coiled‐coil domain‐containing 124

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