Maternal Ribosomes Are Sufficient for Tissue Diversification during Embryonic Development in C. elegans

Cenik, Elif Sarinay; Meng, Xuefeng; Tang, Ningning; Hall, Richard Nelson; Arribere, Joshua A.; Cenik, Can; Jin, Yishi; Fire, Andrew

doi:10.1016/j.devcel.2019.01.019

Cited by 40 publications

(43 citation statements)

References 124 publications

(121 reference statements)

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“…Protein dynamics is shaped by mRNA and protein half-lives, both of which differ among individual transcripts and proteins but also exhibit a tissue-specific pattern of stability with somewhat higher stability in neuronal tissues (8)(9)(10)(11). A recent study in a genetically well-tractable system, C. elegans (28), and earlier observations in Xenopus embryos (45) suggests that tissue diversification may not rely on ribosomes with a heterogeneous RP pool. Along that line, another study shows that ribosome levels determine the human hematopoietic lineage commitment, while the RP sets remain unchanged (29).…”

Section: Discussionmentioning

confidence: 99%

“…eL38 or uS2 (22,23), posttranslational modifications (24,25), or detachment of ribosome-associated factors (26) provide examples for tissue-and message-specific expression, prompting the debate on whether a specialized ribosome pool may shape tissue development (27). This argument is challenged by recent observations in C. elegans that tissue diversification is efficiently maintained during embryonic development by maternal ribosomes and synthesis of a new distinct pool of ribosomes is not required (28). The argument for heterogeneous ribosomal pools conferring message-specific expression is used to explain the tissue specificity of haploinsufficiencies associated with germline mutations disrupting one copy of RP genes in a type of ribosomopathies (14,27).…”

Section: Significancementioning

confidence: 99%

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Invariable stoichiometry of ribosomal proteins in mouse brain tissues with aging

Amirbeigiarab

Kiani

Sanchez

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Across phyla, the ribosomes—the central molecular machines for translation of genetic information—exhibit an overall preserved architecture and a conserved functional core. The natural heterogeneity of the ribosome periodically phases a debate on their functional specialization and the tissue-specific variations of the ribosomal protein (RP) pool. Using sensitive differential proteomics, we performed a thorough quantitative inventory of the protein composition of ribosomes from 3 different mouse brain tissues, i.e., hippocampus, cortex, and cerebellum, across various ages, i.e., juvenile, adult, and middle-aged mouse groups. In all 3 brain tissues, in both monosomal and polysomal ribosome fractions, we detected an invariant set of 72 of 79 core RPs, RACK1 and 2 of the 8 RP paralogs, the stoichiometry of which remained constant across different ages. The amount of a few RPs punctually varied in either one tissue or one age group, but these fluctuations were within the tight bounds of the measurement noise. Further comparison with the ribosomes from a high-metabolic-rate organ, e.g., the liver, revealed protein composition identical to that of the ribosomes from the 3 brain tissues. Together, our data show an invariant protein composition of ribosomes from 4 tissues across different ages of mice and support the idea that functional heterogeneity may arise from factors other than simply ribosomal protein stoichiometry.

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Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

Invariable stoichiometry of ribosomal proteins in mouse brain tissues with aging

Amirbeigiarab

Kiani

Sanchez

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…In either case, however, it would imply that only a subset of translating ribosomes are affected, since the majority of proteins are present at similar levels in both cell lines. Specialised ribosomes have been described in a variety of organisms [59][60][61][62], but have not yet been reported for trypanosomes. Interestingly, Alba4 was mainly present in the free RNA fractions of both AnTat 90-13 and KO cells on day 2, and then shifted progressively to the early polysomes on day 4 and the late polysomes on day 8, implying that its main role is in fully differentiated cells.…”

Section: Plos Pathogensmentioning

confidence: 99%

An Alba-domain protein required for proteome remodelling during trypanosome differentiation and host transition

et al. 2021

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The transition between hosts is a challenge for digenetic parasites as it is unpredictable. For Trypanosoma brucei subspecies, which are disseminated by tsetse flies, adaptation to the new host requires differentiation of stumpy forms picked up from mammals to procyclic forms in the fly midgut. Here we show that the Alba-domain protein Alba3 is not essential for mammalian slender forms, nor is it required for differentiation of slender to stumpy forms in culture or in mice. It is crucial, however, for the development of T. brucei procyclic forms during the host transition. While steady state levels of mRNAs in differentiating cells are barely affected by the loss of Alba3, there are major repercussions for the proteome. Mechanistically, Alba3 aids differentiation by rapidly releasing stumpy forms from translational repression and stimulating polysome formation. In its absence, parasites fail to remodel their proteome appropriately, lack components of the mitochondrial respiratory chain and show reduced infection of tsetse. Interestingly, Alba3 and the closely related Alba4 are functionally redundant in slender forms, but Alba4 cannot compensate for the lack of Alba3 during differentiation from the stumpy to the procyclic form. We postulate that Alba-domain proteins play similar roles in regulating translation in other protozoan parasites, in particular during life-cycle and host transitions.

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“…Yet it is still unclear how and why a cell would produce such heterogeneity given the complex and energy expensive nature of ribosome biogenesis (Klinge and Woolford, 2019;Peña et al, 2017). Potentially supporting this interpretation, a recent study found that maternal ribosomes are sufficient for embryogenesis in C. elegans (Cenik et al, 2019), meaning that functional ribosome heterogeneity in embryonic cell types must occur after assembly and transport. Such post-synthesis heterogeneity may be selected and functional, but it has also not been ruled out whether natural ribosome deficiency of eS25 is a consequence of aberrant translation events.…”

Section: Discussionmentioning

confidence: 99%

A memory of RPS25 loss drives resistance phenotypes

Johnson

Flynn

Lapointe

et al. 2019

Preprint

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In order to maintain cellular protein homeostasis, ribosomes are safeguarded against dysregulation by myriad processes. Remarkably, many cell types can withstand the genetic disruption of numerous ribosomal protein genes, indicating that select ribosome variants can sustain cellular life. Genetic alterations of ribosomal protein genes have been further linked to diverse cellular phenotypes and human disease, yet the direct and indirect consequences of sustained alterations in ribosomal protein levels are poorly understood. To address this knowledge gap, we studied in vitro and cellular consequences that follow genetic knockout of the small subunit ribosomal proteins RPS25 or RACK1 in a human haploid cell line. To our surprise, we found that multiple cellular phenotypes previously assumed to result from a direct effect on translation were instead caused by indirect effects. During characterization of ribosomes isolated from the RPS25 knockout cell line, we discovered a partial remodeling of the large subunit via the ribosomal protein paralog eL22L1. Upon further examination, we found that RPS25 knockout clones display irreversible rewiring of viral-and toxin-resistance phenotypes, suggesting that the cells had undergone a stable transition to a new cell state. This new state appears to drive pleiotropic phenotypes and is characterized by a dramatically altered transcriptome and membrane proteome. By homology-directed repair of a RPS25 knockout cell line, we demonstrate that even when RPS25 expression is rescued at the native genomic locus, cells fail to correct for the phenotypic hysteresis. Our results illustrate how the elasticity of cells to a ribosome perturbation can manifest as specific but indirect phenotypic outcomes. The eukaryotic ribosome is comprised of four strands of rRNA and ~80 ribosomal proteins (RPs)

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Maternal Ribosomes Are Sufficient for Tissue Diversification during Embryonic Development in C. elegans

Cited by 40 publications

References 124 publications

Invariable stoichiometry of ribosomal proteins in mouse brain tissues with aging

Invariable stoichiometry of ribosomal proteins in mouse brain tissues with aging

An Alba-domain protein required for proteome remodelling during trypanosome differentiation and host transition

A memory of RPS25 loss drives resistance phenotypes

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