Changes in the Transcriptome Caused by Mutations in the Ribosomal Protein uS10 Associated with a Predisposition to Colorectal Cancer

Tian, Yueming; Babaylova, Elena S.; Gopanenko, Alexander V.; Tupikin, Alexey E.; Kabilov, Мarsel R.; Malygin, Alexey A.; Карпова, Г. Г.

doi:10.3390/ijms23116174

Cited by 4 publications

(4 citation statements)

References 79 publications

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“…The incidence rate of colorectal cancer(CRC) is the second highest among malignant tumours and the mortality rate is the fourth highest [27] . Since 2016, the incidence rate and mortality rate of CRC have shown an increasing trend.…”

Section: Discussionmentioning

confidence: 99%

Multi-gene models for survival prognosis of colorectal cancer patients

Zhang

et al. 2022

Preprint

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Background The lack of effective prognostic models for colorectal cancer (CRC) makes it crucial to establish a reliable prognostic model for colorectal cancer. The aim of this study was to develop a reliable prognostic model in CRC. Using CRC samples from the TCGA database, a multi-gene combination model was screened for prognosis in CRC patients and the prognostic power of the multi-gene combination model was validated. We screened a multi-gene combination model for risk stratification and prognosis of CRC patients, which is important for individualised clinical treatment and long-term management of colorectal cancer patients. Results To solve these questions, we used data from colorectal cancer patients in the TCGA database to uncover differential genes, screened variables using one-way COX analysis and LASSO regression analysis, and then screened for the polygenic combination most associated with colorectal cancer and assessed its significance on survival events using multi-factor COX analysis and ROC curves to assess polygenic combinations. Finally, using gene enrichment analysis, the polygenic combinations were found to be associated with tRNA biosynthesis, homologous recombination, nucleotide excision repair, ribosome biogenesis in eukaryotes and DNA replication. Conclusions The multi-gene combination (FCGBP, GSTM1, IGLV4-69, IGSF9 and PCOLCE2) model screened in this study is capable of prognosticating colorectal cancer, and the findings of this study could shed new light on the prognosis of colorectal cancer in the clinical setting.

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Section: Discussionmentioning

confidence: 99%

Multi-gene models for survival prognosis of colorectal cancer patients

Zhang

et al. 2022

Preprint

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“…We have recently shown how mutant forms of the uS10 protein, resulting from the expression by HEK293T cells of genetic constructs containing copies of the gene encoding uS10 with mutations authentic to those found in patients with a predisposition to CRC, change the cellular transcriptome [ 11 ]. Using RNA-seq and subsequent bioinformatics analysis, we found that among the limited number of genes expressed differentially in the cells generating mutant uS10 forms, there were upregulated genes directly associated with the progression of CRC (e.g.…”

Section: Introductionmentioning

confidence: 99%

Deficiency of the ribosomal protein uS10 (RPS20) reorganizes human cells translatome according to the abundance, CDS length and GC content of mRNAs

Tian,

Babaylova,

Gopanenko

et al. 2024

Open Biol.

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Ribosomal protein uS10, a product of the RPS20 gene, is an essential constituent of the small (40S) subunit of the human ribosome. Disruptive mutations in its gene are associated with a predisposition to hereditary colorectal carcinoma. Here, using HEK293T cells, we show that a deficiency of this protein leads to a decrease in the level of ribosomes (ribosomal shortage). RNA sequencing of the total and polysome-associated mRNA samples reveals hundreds of genes differentially expressed in the transcriptome (t)DEGs and translatome (p)DEGs under conditions of uS10 deficiency. We demonstrate that the (t)DEG and (p)DEG sets partially overlap, determine genes with altered translational efficiency (TE) and identify cellular processes affected by uS10 deficiency-induced ribosomal shortage. We reveal that translated mRNAs of upregulated (p)DEGs and genes with altered TE in uS10-deficient cells are generally more abundant and that their GC contents are significantly lower than those of the respective downregulated sets. We also observed that upregulated (p)DEGs have longer coding sequences. Based on our findings, we propose a combinatorial model describing the process of reorganization of mRNA translation under conditions of ribosomal shortage. Our results reveal rules according to which ribosomal shortage reorganizes the transcriptome and translatome repertoires of actively proliferating cells.

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“…The next-generation sequencing (NGS) of RNA (RNA-seq) is currently an advanced method for studying changes in the transcriptome and translatome landscapes of cells in response to various stimuli, including the deficiency of individual ribosomal proteins [ 23 , 24 , 25 , 26 , 27 ] or the introduction of specific mutations in them [ 28 ]. Being applied to the analysis of total cellular mRNA and mRNAs translated in polysomes, this method makes it possible to draw conclusions concerning the regulation of expression of individual genes at the levels of transcription and translation, and to evaluate their translational efficiencies.…”

Section: Introductionmentioning

confidence: 99%

Mutation at the Site of Hydroxylation in the Ribosomal Protein uL15 (RPL27a) Causes Specific Changes in the Repertoire of mRNAs Translated in Mammalian Cells

Zolotenkova

Gopanenko

Tupikin

et al. 2023

IJMS

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Ribosomal protein uL15 (RPL27a) carries a specific modification, hydroxylation, at the His39 residue, which neighbors the CCA terminus of the E-site-bound tRNA at the mammalian ribosome. Under hypoxia, the level of hydroxylation of this protein decreases. We transiently transfected HEK293T cells with constructs expressing wild-type uL15 or mutated uL15 (His39Ala) incapable of hydroxylation, and demonstrated that ribosomes containing both proteins are competent in translation. By applying RNA-seq to the total cellular and polysome-associated mRNAs, we identified differentially expressed genes (DEGs) in cells containing exogenous uL15 or its mutant form. Analyzing mRNA features of up- and down-regulated DEGs, we found an increase in the level of more abundant mRNAs and shorter CDSs in cells with uL15 mutant for both translated and total cellular mRNAs. The level of longer and rarer mRNAs, on the contrary, decreased. Our data show how ribosome heterogeneity can change the composition of the translatome and transcriptome, depending on the properties of the translated mRNAs.

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Changes in the Transcriptome Caused by Mutations in the Ribosomal Protein uS10 Associated with a Predisposition to Colorectal Cancer

Cited by 4 publications

References 79 publications

Multi-gene models for survival prognosis of colorectal cancer patients

Multi-gene models for survival prognosis of colorectal cancer patients

Deficiency of the ribosomal protein uS10 (RPS20) reorganizes human cells translatome according to the abundance, CDS length and GC content of mRNAs

Mutation at the Site of Hydroxylation in the Ribosomal Protein uL15 (RPL27a) Causes Specific Changes in the Repertoire of mRNAs Translated in Mammalian Cells

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