PDCD2 functions as an evolutionarily conserved chaperone dedicated for the 40S ribosomal protein uS5 (RPS2)

Landry-Voyer, Anne-Marie; Bergeron, David Μ.; Yague-Sanz, Carlo; Baker, Breac; Bachand, François

doi:10.1093/nar/gkaa1108

“…Purification of Enp1-FTP particles from cells in which Tsr4-AID was depleted for two hours revealed that both Rrp12 and Bud23 accumulated in the absence of Tsr4 (Figure S5D). Because Tsr4 facilitates Rps2 expression (Black et al 2019;Rössler et al 2019;Landry-Voyer et al 2020), this result further supports the notion that Rps2 is needed for the release of Bud23 from the pre-40S.…”

Section: Resultssupporting

confidence: 78%

“…Depletion of Tsr4, the chaperone of Rps2, also causes Bud23 to accumulate on pre-40S. We and others recently identified Tsr4 as an essential, dedicated chaperone that facilitates Rps2 expression (Black et al 2019;Rössler et al 2019;Landry-Voyer et al 2020). To further support the idea that Rps2 is needed for Bud23 release, we asked if Bud23 accumulates on pre-40S particles in Tsr4-depleted cells.…”

Section: Resultsmentioning

confidence: 93%

Release of the ribosome biogenesis factor Bud23 from small subunit precursors in yeast

Black

¹

,

Johnson

²

2021

Preprint

0

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Ribosomes are the universally conserved ribonucleoprotein complexes that synthesize proteins. The two subunits of the eukaryotic ribosome are produced through a quasi-independent assembly-line-like pathway involving the hierarchical actions of numerous trans-acting biogenesis factors and the incorporation of ribosomal proteins. The factors work together to shape the nascent subunits through a series of intermediate states into their functional architectures. The earliest intermediate of the small subunit (SSU or 40S) is the SSU Processome which is subsequently transformed into the pre-40S intermediate. This transformation is, in part, facilitated by the binding of the methyltransferase Bud23. How Bud23 is released from the resultant pre-40S is not known. The ribosomal proteins Rps0, Rps2, and Rps21, termed the Rps0-cluster proteins, and several biogenesis factors are known to bind the pre-40S around the time that Bud23 is released, suggesting that one or more of these factors induce Bud23 release. Here, we systematically examined the requirement of these factors for the release of Bud23 from pre-40S particles. We found that the Rps0-cluster proteins are needed but not sufficient for Bud23 release. The atypical kinase/ATPase Rio2 shares a binding site with Bud23 and is thought to be recruited to pre-40S after the Rps0-cluster proteins. Depletion of Rio2 prevented the release of Bud23 from the pre-40S. More importantly, the addition of recombinant Rio2 to pre-40S particles affinity-purified from Rio2-depleted cells was sufficient for Bud23 release in vitro. The ability of Rio2 to displace Bud23 was independent of nucleotide hydrolysis. We propose a novel role for Rio2 in which its binding to the pre-40S actively displaces Bud23 from the pre-40S, and we suggest a model in which the binding of the Rps0-cluster proteins and Rio2 promote the release of Bud23.

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“…Purification of Enp1-FTP particles from cells in which Tsr4-AID was depleted for two hours revealed that both Rrp12 and Bud23 accumulated in the absence of Tsr4 (Figure S5D). Because Tsr4 promotes Rps2 expression (Black et al 2019;Rössler et al 2019;Landry-Voyer et al 2020), this result further supports the notion that Rps2 is needed for the release of Bud23 from the pre-40S.…”

Section: Depletion Of Tsr4 Also Causes Bud23 To Accumulate On Pre-40ssupporting

confidence: 78%

Release of the ribosome biogenesis factor Bud23 from small subunit precursors in yeast

Black

¹

,

Johnson

²

2021

RNA

View full text Add to dashboard Cite

Ribosomes are the universally conserved ribonucleoprotein complexes that synthesize proteins. The two subunits of the eukaryotic ribosome are produced through a quasi-independent assembly-line-like pathway involving the hierarchical actions of numerous trans-acting biogenesis factors and the incorporation of ribosomal proteins. The factors work together to shape the nascent subunits through a series of intermediate states into their functional architectures. The earliest intermediate of the small subunit (SSU or 40S) is the SSU Processome which is subsequently transformed into the pre-40S intermediate. This transformation is, in part, facilitated by the binding of the methyltransferase Bud23. How Bud23 is released from the resultant pre-40S is not known. The ribosomal proteins Rps0, Rps2, and Rps21, termed the Rps0-cluster proteins, and several biogenesis factors are known to bind the pre-40S around the time that Bud23 is released, suggesting that one or more of these factors induce Bud23 release. Here, we systematically examined the requirement of these factors for the release of Bud23 from pre-40S particles. We found that the Rps0-cluster proteins are needed but not sufficient for Bud23 release. The atypical kinase/ATPase Rio2 shares a binding site with Bud23 and is thought to be recruited to pre-40S after the Rps0-cluster proteins. Depletion of Rio2 prevented the release of Bud23 from the pre-40S. More importantly, the addition of recombinant Rio2 to pre-40S particles affinity-purified from Rio2-depleted cells was sufficient for Bud23 release in vitro. The ability of Rio2 to displace Bud23 was independent of nucleotide hydrolysis. We propose a novel role for Rio2 in which its binding to the pre-40S actively displaces Bud23 from the pre-40S, and we suggest a model in which the binding of the Rps0-cluster proteins and Rio2 promote the release of Bud23.

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“…KEGG analysis showed the SRMS co-expression genes mainly enrichment in the ribosomal, proteasomal, oxidative phosphorylation, and DNA replication pathways. Ribosomes, comprised of ribonucleoprotein and non-coding ribosomal RNAs in eukaryotes, are conserved molecular structures required for protein synthesis [ 35 ]. Cancer development and progression are associated with ribosomal dysregulation, which affects the expression of key factors involved in tumorigenesis [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

The possible role of SRMS in colorectal cancer by bioinformatics analysis

Zhang

¹

,

Liu

²

,

Feng

³

et al. 2021

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Background Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristoylation sites (SRMS) is a non-receptor tyrosine kinase that has been found to be overexpressed in various tumors. However, the role of SRMS in colorectal cancer (CRC) has not been well established. Methods We evaluated the expression levels of SRMS in CRC using GEPIA, Oncomine, and HPA datasets. Survival information and gene expression data of CRC were obtained from The Cancer Genome Atlas (TCGA). Then, the association between SRMS and clinicopathological features was analyzed using UALCAN dataset. LinkedOmics was used to determine co-expression and functional networks associated with SRMS. Besides, we used TISIDB to assess the correlation between SRMS and immune signatures, including tumor-infiltrating immune cells and immunomodulators. Lastly, protein-protein interaction network (PPI) was established and the function enrichment analysis of the SRMS-associated immunomodulators and immune cell marker genes were performed using the STRING portal. Results Compared to normal colorectal tissues, SRMS was found to be overexpressed in CRC tissues, which was correlated with a poor prognosis. In colon adenocarcinoma (COAD), the expression levels of SRMS are significantly correlated with pathological stages and nodal metastasis status. Functional network analysis suggested that SRMS regulates intermediate filament-based processes, protein autophosphorylation, translational initiation, and elongation signaling through pathways involving ribosomes, proteasomes, oxidative phosphorylation, and DNA replication. In addition, SRMS expression was correlated with infiltrating levels of CD4+ T cells, CD56dim, MEM B, Neutrophils, Th2, Th17, and Act DC. The gene ontology (GO) analysis of SRMS-associated immunomodulators and immune cell marker genes showed that they were mainly enriched in the immune microenvironment molecule-related signals. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of these genes indicated that they are involved in multiple cancer-related pathways. Conclusions SRMS is a promising prognostic biomarker and potential therapeutic target for CRC patients. In particular, SRMS regulates CRC progression by modulating cytokine-cytokine receptor interaction, chemokines, IL-17, and intestinal immune networks for IgA production signaling pathways among others. However, more studies are needed to validate these findings.

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PDCD2 functions as an evolutionarily conserved chaperone dedicated for the 40S ribosomal protein uS5 (RPS2)

Cited by 18 publications

References 59 publications

Release of the ribosome biogenesis factor Bud23 from small subunit precursors in yeast

Release of the ribosome biogenesis factor Bud23 from small subunit precursors in yeast

Release of the ribosome biogenesis factor Bud23 from small subunit precursors in yeast

The possible role of SRMS in colorectal cancer by bioinformatics analysis

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