RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit

Cerezo, Emilie L.; Houlès, Thibault; Lié, Oriane; Sarthou, Marie-Kerguelen; Audoynaud, Charlotte; Lavoie, Geneviève; Halladjian, Maral; Cantaloube, Sylvain; Froment, Carine; Burlet‐Schiltz, Odile; Henry, Y.; Roux, Philippe P.; Henras, Anthony K.; Roméo, Yves

doi:10.1371/journal.pgen.1009583

Cited by 10 publications

(7 citation statements)

References 84 publications

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“…RIOK2 belongs to the family of RIO kinases, which comprises three members: RIOK1, RIOK2, and RIOK3 (LaRonde- LeBlanc and Wlodawer, 2005). RIO kinases play a role in pre-ribosomal RNA processing and the biogenesis of ribosomes (Cerezo et al, 2021). The miRNA-TF-mRNA regulatory network.…”

Section: Discussionmentioning

confidence: 99%

“…RIOK2 belongs to the family of RIO kinases, which comprises three members: RIOK1, RIOK2, and RIOK3 ( LaRonde-LeBlanc and Wlodawer, 2005 ). RIO kinases play a role in pre-ribosomal RNA processing and the biogenesis of ribosomes ( Cerezo et al, 2021 ). The role of RIO kinases in cancer has been increasingly investigated, with the RIOK2 ATPase activity essential for cell survival.…”

Section: Discussionmentioning

confidence: 99%

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Identification of common genes and pathways between type 2 diabetes and COVID-19

Wang,

Li,

et al. 2024

Front. Genet.

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Background:Numerous studies have reported a high incidence and risk of severe illness due to coronavirus disease 2019 (COVID-19) in patients with type 2 diabetes (T2DM). COVID-19 patients may experience elevated or decreased blood sugar levels and may even develop diabetes. However, the molecular mechanisms linking these two diseases remain unclear. This study aimed to identify the common genes and pathways between T2DM and COVID-19.Methods:Two public datasets from the Gene Expression Omnibus (GEO) database (GSE95849 and GSE164805) were analyzed to identify differentially expressed genes (DEGs) in blood between people with and without T2DM and COVID-19. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the common DEGs. A protein-protein interaction (PPI) network was constructed to identify common genes, and their diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analysis. Validation was performed on the GSE213313 and GSE15932 datasets. A gene co-expression network was constructed using the GeneMANIA database to explore interactions among core DEGs and their co-expressed genes. Finally, a microRNA (miRNA)-transcription factor (TF)-messenger RNA (mRNA) regulatory network was constructed based on the common feature genes.Results:In the GSE95849 and GSE164805 datasets, 81 upregulated genes and 140 downregulated genes were identified. GO and KEGG enrichment analyses revealed that these DEGs were closely related to the negative regulation of phosphate metabolic processes, the positive regulation of mitotic nuclear division, T-cell co-stimulation, and lymphocyte co-stimulation. Four upregulated common genes (DHX15, USP14, COPS3, TYK2) and one downregulated common feature gene (RIOK2) were identified and showed good diagnostic accuracy for T2DM and COVID-19. The AUC values of DHX15, USP14, COPS3, TYK2, and RIOK2 in T2DM diagnosis were 0.931, 0.917, 0.986, 0.903, and 0.917, respectively. In COVID-19 diagnosis, the AUC values were 0.960, 0.860, 1.0, 0.9, and 0.90, respectively. Validation in the GSE213313 and GSE15932 datasets confirmed these results. The miRNA-TF-mRNA regulatory network showed that TYH2 was targeted by PITX1, PITX2, CRX, NFYA, SREBF1, RELB, NR1L2, and CEBP, whereas miR-124-3p regulates THK2, RIOK2, and USP14.Conclusion:We identified five common feature genes (DHX15, USP14, COPS3, TYK2, and RIOK2) and their co-regulatory pathways between T2DM and COVID-19, which may provide new insights for further molecular mechanism studies.

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Section: Discussionmentioning

confidence: 99%

“…RIOK2 belongs to the family of RIO kinases, which comprises three members: RIOK1, RIOK2, and RIOK3 ( LaRonde-LeBlanc and Wlodawer, 2005 ). RIO kinases play a role in pre-ribosomal RNA processing and the biogenesis of ribosomes ( Cerezo et al, 2021 ). The role of RIO kinases in cancer has been increasingly investigated, with the RIOK2 ATPase activity essential for cell survival.…”

Section: Discussionmentioning

confidence: 99%

Identification of common genes and pathways between type 2 diabetes and COVID-19

Wang,

Li,

et al. 2024

Front. Genet.

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“…So, we speculated that it might play a crucial role via interacting with RIOK2 for responses to DON exposure. A recent study suggested that RIOK2 is a new target of the MAPK-activated kinase RSK [ 39 ]. As components of the MAPK signaling pathway, ERK and JNK are associated with the regulation of cell survival and death [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Analysis of RIOK2 Functions in Mediating the Toxic Effects of Deoxynivalenol in Porcine Intestinal Epithelial Cells

Gao

Fan

et al. 2022

IJMS

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Deoxynivalenol (DON) is a type of mycotoxin that threatens human and livestock health. Right open reading frame kinase 2 (RIOK2) is a kinase that has a pivotal function in ribosome maturation and cell cycle progression. This study aims to clarify the role of the RIOK2 gene in DON-induced cytotoxicity regulation in porcine intestinal epithelial cells (IPEC-J2). Cell viability assay and flow cytometry showed that the knockdown of RIOK2 inhibited proliferation and induced apoptosis, cell cycle arrest, and oxidative stress in DON-induced IPEC-J2. Then, transcriptome profiling identified candidate genes and pathways that closely interacted with both DON cytotoxicity regulation and RIOK2 expression. Furthermore, RIOK2 interference promoted the activation of the MAPK signaling pathway by increasing the phosphorylation of ERK and JNK. Additionally, we performed the dual-luciferase reporter and ChIP assays to elucidate that the expression of RIOK2 was influenced by the binding of transcription factor Sp1 with the promoter region. Briefly, the reduced expression of the RIOK2 gene exacerbates the cytotoxic effects induced by DON in IPEC-J2. Our findings provide insights into the control strategies for DON contamination by identifying functional genes and effective molecular markers.

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“…Cell lysates were prepared as previously described 77 . Briefly, cells were washed three times with ice-cold phosphate-buffered saline (PBS) and lysed in RIPA or BLB buffer (10 mM K 3 PO 4 , 1 mM EDTA, 5 mM EGTA, 10 mM MgCl 2 , 50 mM β-glycerophosphate, 0.5% Nonidet P-40, 0.1% Brij 35, 0.1% deoxycholic acid), complemented with 1 mM sodium orthovanadate [Na 3 VO 4 ], 1 mM phenylmethylsulfonyl fluoride, and a cOmplete protease inhibitor cocktail tablet (Roche).…”

Section: Methodsmentioning

confidence: 99%

CDK12 is hyperactivated and a synthetic-lethal target in BRAF-mutated melanoma

et al. 2022

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Melanoma is the deadliest form of skin cancer and considered intrinsically resistant to chemotherapy. Nearly all melanomas harbor mutations that activate the RAS/mitogen-activated protein kinase (MAPK) pathway, which contributes to drug resistance via poorly described mechanisms. Herein we show that the RAS/MAPK pathway regulates the activity of cyclin-dependent kinase 12 (CDK12), which is a transcriptional CDK required for genomic stability. We find that melanoma cells harbor constitutively high CDK12 activity, and that its inhibition decreases the expression of long genes containing multiple exons, including many genes involved in DNA repair. Conversely, our results show that CDK12 inhibition promotes the expression of short genes with few exons, including many growth-promoting genes regulated by the AP-1 and NF-κB transcription factors. Inhibition of these pathways strongly synergize with CDK12 inhibitors to suppress melanoma growth, suggesting promising drug combinations for more effective melanoma treatment.

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RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit

Cited by 10 publications

References 84 publications

Identification of common genes and pathways between type 2 diabetes and COVID-19

Identification of common genes and pathways between type 2 diabetes and COVID-19

Analysis of RIOK2 Functions in Mediating the Toxic Effects of Deoxynivalenol in Porcine Intestinal Epithelial Cells

CDK12 is hyperactivated and a synthetic-lethal target in BRAF-mutated melanoma

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