Human Ribosomal Proteins RPeL27, RPeL43, and RPeL41 Are Upregulated in Nasopharyngeal Carcinoma Cell Lines

Apart from their canonical role in ribosome biogenesis, there is increasing evidence of ribosomal protein genes’ involvement in various cancers. A previous study by us revealed significant differential expression of three ribosomal protein genes (RPeL27, RPeL41, and RPeL43) between cell lines derived from tumor and normal nasopharyngeal epithelium. However, the results therein were based on a semiquantitative assay, thus preliminary in nature. Herein, we provide findings of a deeper analysis of these three genes in the context to nasopharyngeal carcinoma (NPC) tumorigenesis. Their expression patterns were analyzed in a more quantitative manner at transcript level. Their protein expression levels were also investigated. We showed results that are contrary to previous report. Rather than downregulation, these genes were significantly overexpressed in NPC cell lines compared to normal control at both transcript and protein levels. Nevertheless, their association with NPC has been established. Immunoprecipitation pulldown assays indicate the plausible interaction of either RPeL27 or RPeL43 with POTEE/TUBA1A and ACTB/ACTBL2 complexes. In addition, RPeL43 is shown to bind with MRAS and EIF2S1 proteins in a NPC cell line (HK1). Our findings support RPeL27, RPeL41, and RPeL43 as potential markers of NPC and provide insights into the interaction targets of RPeL27 and RPeL43 proteins.

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TheuS8,uS4,eS31, anduL14Ribosomal Protein Genes Are Dysregulated in Nasopharyngeal Carcinoma Cell Lines

BioMed Research International ◽

10.1155/2017/4876954 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Edmund Ui-Hang Sim ◽

Kher-Lee Ng ◽

Choon-Weng Lee ◽

Kumaran Narayanan

Keyword(s):

Nasopharyngeal Carcinoma ◽

Ribosomal Protein ◽

Cell Lines ◽

Ribosomal Proteins ◽

Expression Profiles ◽

Nasopharyngeal Cancer ◽

Epithelial Cell Line ◽

Ribosomal Protein Genes ◽

Carcinoma Cell Lines ◽

Nasopharyngeal Epithelial Cell

The association of ribosomal proteins with carcinogenesis of nasopharyngeal carcinoma (NPC) has been established in a limited subset of ribosomal protein genes. To date, three ribosomal protein genes,eL27 (L27),eL41 (L41), andeL43 (L37a), have been found to be differentially expressed in cell lines derived from NPC tumors. This raises the possibility of more ribosomal protein genes that could be associated with NPC. In this study, we investigated the expression profiles of eight ribosomal protein genes,uS8 (S8), uS4 (S9), eS31 (S27a), eL6 (L6), eL18 (L18), uL14 (L23), eL24 (L24), andeL30 (L30), in six NPC-derived cell lines(HONE-1, SUNE1, HK1, TW01, TW04, and C666-1). Their expression levels were compared with that of a nonmalignant nasopharyngeal epithelial cell line (NP69) using quantitative real-time PCR (RT-qPCR) assay. Of the eight genes studied, the expressions of four ribosomal protein genesuS8 (S8), uS4 (S9), eS31 (S27a),anduL14 (L23)were found to be significantly downregulated in NPC cell lines relative to NP69. Our findings provide novel empirical evidence of these four ribosomal protein genes as NPC-associated genetic factors and reinforce the relevance of ribosomal proteins in the carcinogenesis of nasopharyngeal cancer.

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A Novel Drosophila Minute Locus Encodes Ribosomal Protein S13

Genetics ◽

10.1093/genetics/143.2.877 ◽

1996 ◽

Vol 143 (2) ◽

pp. 877-885 ◽

Cited By ~ 1

Author(s):

Stein Saeboe-Larssen ◽

Andrew Lambertsson

Keyword(s):

Ribosomal Protein ◽

Ribosomal Proteins ◽

Transcript Level ◽

P Element ◽

Ribosomal Protein Genes ◽

Loss Of Function ◽

Wild Type ◽

Sequence Analyses ◽

Slow Development ◽

Ribosomal Protein S13

Abstract Minutes comprise >50 phenotypically similar Drosophila mutations believed to affect ribosomal protein genes. Common traits of the Minute phenotype are short and thin bristles, slow development, and recessive lethality. To further investigate the proposed Minute to ribosomal protein correspondence, loss-of-function Minute mutations were induced by P-element mutagenesis. Here, we report a previously undescribed Minute locus that maps to 32A on chromosome 2L; this Minute allele is named P{lac-W}M(2)32A1 and the gene M(2)32A. Flies heterozygous for P{lacW}M(2)32A1 have a medium Minute phenotype. The gene interrupted by the P-element insertion was cloned. Sequence analyses revealed that it encodes the Drosophila homologue of eukaryotic ribosomal protein S13. It is a singlecopy gene and the level of RPS13 transcript is reduced to ~50% in P{lacW}M(2)32A1 heterozygotes. Both transcript level and phenotype are restored to wild type by remobilizing the P element, demonstrating that the mutation is caused by insertion of the P-element construct. These results further strengthen the notion that Minutes encode ribosomal proteins and demonstrate that P-element mutagenesis is a fruitful approach to use in these studies.

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Control of ribosomal protein synthesis by the Microprocessor complex

Science Signaling ◽

10.1126/scisignal.abd2639 ◽

2021 ◽

Vol 14 (671) ◽

pp. eabd2639

Author(s):

Xuan Jiang ◽

Amit Prabhakar ◽

Stephanie M. Van der Voorn ◽

Prajakta Ghatpande ◽

Barbara Celona ◽

...

Keyword(s):

Protein Synthesis ◽

Ribosomal Protein ◽

Nuclear Export ◽

Ribosomal Proteins ◽

Ribosome Biogenesis ◽

Cellular Growth ◽

Ribosomal Protein Genes ◽

Erythroid Progenitors ◽

Microprocessor Complex ◽

Ribosomal Protein Synthesis

Ribosome biogenesis in eukaryotes requires the coordinated production and assembly of 80 ribosomal proteins and four ribosomal RNAs (rRNAs), and its rate must be synchronized with cellular growth. Here, we showed that the Microprocessor complex, which mediates the first step of microRNA processing, potentiated the transcription of ribosomal protein genes by eliminating DNA/RNA hybrids known as R-loops. Nutrient deprivation triggered the nuclear export of Drosha, a key component of the Microprocessor complex, and its subsequent degradation by the E3 ubiquitin ligase Nedd4, thereby reducing ribosomal protein production and protein synthesis. In mouse erythroid progenitors, conditional deletion of Drosha led to the reduced production of ribosomal proteins, translational inhibition of the mRNA encoding the erythroid transcription factor Gata1, and impaired erythropoiesis. This phenotype mirrored the clinical presentation of human “ribosomopathies.” Thus, the Microprocessor complex plays a pivotal role in synchronizing protein synthesis capacity with cellular growth rate and is a potential drug target for anemias caused by ribosomal insufficiency.

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Mild temperature shock alters the transcription of a discrete class of Saccharomyces cerevisiae genes

Molecular and Cellular Biology ◽

10.1128/mcb.3.3.457-465.1983 ◽

1983 ◽

Vol 3 (3) ◽

pp. 457-465

Author(s):

C H Kim ◽

J R Warner

Keyword(s):

Saccharomyces Cerevisiae ◽

Ribosomal Protein ◽

Ribosomal Proteins ◽

Temperature Shift ◽

Restrictive Temperature ◽

Ribosomal Protein Genes ◽

Wild Type ◽

Temperature Shock ◽

Mild Temperature ◽

Mutant Cells

In Saccharomyces cerevisiae the synthesis of ribosomal proteins declines temporarily after a culture has been subjected to a mild temperature shock, i.e., a shift from 23 to 36 degrees C, each of which support growth. Using cloned genes for several S. cerevisiae ribosomal proteins, we found that the changes in the synthesis of ribosomal proteins parallel the changes in the concentration of mRNA of each. The disappearance and reappearance of the mRNA is due to a brief but severe inhibition of the transcription of each of the ribosomal protein genes, although the total transcription of mRNA in the cells is relatively unaffected by the temperature shock. The precisely coordinated response of these genes, which are scattered throughout the genome, suggests that either they or the enzyme which transcribes them has unique properties. In certain S. cerevisiae mutants, the synthesis of ribosomal proteins never recovers from a temperature shift. Yet both the decline and the resumption of transcription of these genes during the 30 min after the temperature shift are indistinguishable from those in wild-type cells. The failure of the mutant cells to grow at the restrictive temperature appears to be due to their inability to process the RNA transcribed from genes which have introns (Rosbash et al., Cell 24:679-686, 1981), a large proportion of which appear to be ribosomal protein genes.

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Morpho-physiological and gene expression responses of wheat by Aegilops cylindrica amphidiploids to salt stress

10.1101/2020.06.07.139220 ◽

2020 ◽

Author(s):

Razieh Kiani ◽

Ahmad Arzani ◽

S. A. M. Mirmohammady Meibody ◽

Mehdi Rahimmalek ◽

Khadijeh Razavi

Keyword(s):

Salt Stress ◽

Expression Patterns ◽

Ion Homeostasis ◽

Transcript Level ◽

Salt Tolerant ◽

Quantitative Real Time Pcr ◽

Aegilops Cylindrica ◽

Significant Differential Expression ◽

Lower Root ◽

Vacuolar Sequestration

AbstractAegilops cylindrica Host is one of the most salt-tolerant species in the Triticeae tribe. Amphidiploid plants derived from hybridization of ‘Roshan’ × Aegilops cylindrica and ‘Chinese Spring’ × Ae. cylindrica genotypes contrasting in salt tolerance were assessed for their morpho-physiological responses and the expression patterns of two genes related to ion homeostasis under 250 mM NaCl. Results showed that salt stress caused significant declines in both their morphological and phenological traits. Moreover, salt stress reduced not only their chlorophyll content but also their root and shoot K contents and K/Na ratios, while it led to significant enhancements in the remaining traits. Similar to Ae. cylindrica, the amphidiploids subjected to salt stress exhibited significantly higher H2O2 levels, root and shoot K contents, and root and shoot K/Na ratios accompanied by lower root and shoot Na contents and MDA concentrations when compared with the same traits in the wheat parents. Quantitative Real-Time PCR showed significant differential expression patterns of the NHX1 and HKT1;5 genes between the amphidiploids and their parents. The transcript level of HKT1;5 was found to be higher in the roots than in the shoots of both the amphidiploids and Ae. cylindrica while NHX1 exhibited a higher expression in the shoot tissues. The consistency of these data provides compelling support for the hypothesis that active exclusion of Na from the roots and elevated vacuolar sequestration of Na in the leaves might explain the declining Na levels in the shoots and roots of both the amphidiploids and Ae. cylindrica relative to those measured in wheat parents. It is concluded that the hybridized amphiploids are potentially valuable resources for salt improvement in bread wheat through the backcrossing approach.

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Plant trait heterosis is quantitatively associated with expression heterosis of the plastid ribosomal proteins

10.1101/2021.02.16.431485 ◽

2021 ◽

Author(s):

Devon Birdseye ◽

Laura A. de Boer ◽

Hua Bai ◽

Peng Zhou ◽

Zhouxin Shen ◽

...

Keyword(s):

Plant Height ◽

Ribosomal Proteins ◽

Protein Complexes ◽

Expression Patterns ◽

Ethylene Biosynthesis ◽

Hybrid Vigor ◽

Maize Hybrids ◽

Protein Levels ◽

Plant Trait ◽

Elevated Expression

AbstractThe use of hybrids is widespread in agriculture, yet the molecular basis for hybrid vigor (heterosis) remains obscure. To identify molecular components that may contribute to the known higher photosynthetic capacity of maize hybrids, we generated paired datasets of the proteomes and transcriptomes from leaf tissues of maize hybrids and their inbred parents. Expression patterns in the hybrids were semi-dominant to overdominant for subunits of the digenomic protein complexes required for the light reactions of photosynthesis and for chloroplast protein synthesis; nuclear and plastid-encoded subunits were elevated similarly. These patterns were not mirrored in the nuclear transcriptomes. We compared growth to transcript and protein levels of multiple hybrids with varying levels of heterosis. Expression heterosis (hybrid/mid-parent expression levels) of chloroplast ribosomal proteins and of nuclear transcripts for the photosynthetic light reactions was positively correlated with plant height heterosis (hybrid/mid-parent plant height). Ethylene biosynthetic enzymes were expressed below mid-parent levels in the hybrids, and the ethylene biosynthesis mutant acs2/acs6 partially phenocopied the hybrid proteome, indicating that a reduction in ethylene biosynthesis may be upstream of the elevated expression of photosynthetic and ribosomal proteins in chloroplasts of hybrids.

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The yeast omnipotent suppressor SUP46 encodes a ribosomal protein which is a functional and structural homolog of the Escherichia coli S4 ram protein.

Genetics ◽

10.1093/genetics/132.2.375 ◽

1992 ◽

Vol 132 (2) ◽

pp. 375-386 ◽

Cited By ~ 1

Author(s):

A Vincent ◽

S W Liebman

Keyword(s):

Escherichia Coli ◽

Ribosomal Protein ◽

Dna Sequences ◽

Ribosomal Proteins ◽

Amino Acid Sequences ◽

Ribosomal Protein Genes ◽

Significant Homology ◽

A Cell ◽

Functional Equivalent ◽

Ribosomal Protein S13

Abstract The accurate synthesis of proteins is crucial to the existence of a cell. In yeast, several genes that affect the fidelity of translation have been identified (e.g., omnipotent suppressors, antisuppressors and allosuppressors). We have found that the dominant omnipotent suppressor SUP46 encodes the yeast ribosomal protein S13. S13 is encoded by two similar genes, but only the sup46 copy of the gene is able to fully complement the recessive phenotypes of SUP46 mutations. Both copies of the S13 genes contain introns. Unlike the introns of other duplicated ribosomal protein genes which are highly diverged, the duplicated S13 genes have two nearly identical DNA sequences of 25 and 31 bp in length within their introns. The SUP46 protein has significant homology to the S4 ribosomal protein in prokaryotic-type ribosomes. S4 is encoded by one of the ram (ribosomal ambiguity) genes in Escherichia coli which are the functional equivalent of omnipotent suppressors in yeast. Thus, SUP46 and S4 demonstrate functional as well as sequence conservation between prokaryotic and eukaryotic ribosomal proteins. SUP46 and S4 are most similar in their central amino acid sequences. Interestingly, the alterations resulting from the SUP46 mutations and the segment of the S4 protein involved in binding to the 16S rRNA are within this most conserved region.

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Genome-Wide Identification, Evolution and Expression of the Complete Set of Cytoplasmic Ribosomal Protein Genes in Nile Tilapia

International Journal of Molecular Sciences ◽

10.3390/ijms21041230 ◽

2020 ◽

Vol 21 (4) ◽

pp. 1230

Author(s):

Gangqiao Kuang ◽

Wenjing Tao ◽

Shuqing Zheng ◽

Xiaoshuang Wang ◽

Deshou Wang

Keyword(s):

Ribosomal Proteins ◽

Nile Tilapia ◽

Ribosome Biogenesis ◽

Developmental Stages ◽

Expression Profiles ◽

Ribosomal Protein Genes ◽

Expression Levels ◽

Sexually Dimorphic Expression ◽

Complete Set ◽

Almost All

Ribosomal proteins (RPs) are indispensable in ribosome biogenesis and protein synthesis, and play a crucial role in diverse developmental processes. In the present study, we carried out a comprehensive analysis of RPs in chordates and examined the expression profiles of the complete set of 92 cytoplasmic RP genes in Nile tilapia. The RP genes were randomly distributed throughout the tilapia genome. Phylogenetic and syntenic analyses revealed the existence of duplicated RP genes from 2R (RPL3, RPL7, RPL22 and RPS27) and 3R (RPL5, RPL19, RPL22, RPL41, RPLP2, RPS17, RPS19 and RPS27) in tilapia and even more from 4R in common carp and Atlantic salmon. The RP genes were found to be expressed in all tissues examined, but their expression levels differed among different tissues. Gonadal transcriptome analysis revealed that almost all RP genes were highly expressed, and their expression levels were highly variable between ovaries and testes at different developmental stages in tilapia. No sex- and stage-specific RP genes were found. Eleven RP genes displayed sexually dimorphic expression with nine higher in XY gonad and two higher in XX gonad at all stages examined, which were proved to be phenotypic sex dependent. Quantitative real-time PCR and immunohistochemistry ofRPL5b and RPL24 were performed to validate the transcriptome data. The genomic resources and expression data obtained in this study will contribute to a better understanding of RPs evolution and functions in chordates.

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p53 Dependent and Dose Dependent Effects of Rps29 Mutation In the Zebrafish Embryo.

Blood ◽

10.1182/blood.v116.21.1170.1170 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1170-1170

Author(s):

Alison M. Taylor ◽

Jessica M. Humphries ◽

Richard M. White ◽

Ryan D. Murphey ◽

Caroline E. Burns ◽

...

Keyword(s):

Ribosomal Protein ◽

Board Of Directors ◽

Ribosomal Proteins ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Ribosomal Protein Genes ◽

Advisory Committees ◽

Cardinal Vein ◽

Hematopoietic Stem ◽

Equity Ownership

Abstract Abstract 1170 Diamond Blackfan anemia (DBA) is a rare congenital disease characterized by red cell aplasia and craniofacial abnormalities. Ribosomal protein genes are often mutated in patients with this disease, but the mechanism of action is still being investigated. To elucidate the effect of mutations in ribosomal proteins, we are studying a zebrafish rps29 mutant with hematopoietic and endothelial defects. Hematopoietic stem cells (HSCs) in rps29-/- embryos are significantly decreased, as assayed by runx1 and cmyb expression. Although the aorta and posterior cardinal vein form in the mutant, intersomitic vessel formation is affected. To test whether decreased p53 levels can rescue these defects, we crossed fish with mutated p53 into the rps29 background. In rps29-/-;p53-/- embryos, the vascular and HSC phenotypes are rescued, demonstrating that p53 may be required for these effects of rps29 knockdown. We performed a microarray comparing rps29-/- embryos and their siblings to identify genes that are differentially expressed in the mutant. Using gene set enrichment analysis (GSEA), we determined that the list of genes up-regulated in the rps29 mutant is enriched for genes up-regulated by p53 in response to irradiation. Many of the genes identified have known roles in apoptosis and stress response. We have also identified genes whose expression correlates with the number of wildtype copies of rps29. Orthopedia homolog a (otpa), which is specifically expressed in forebrain and hindbrain tissues at 24 hours post fertilization (hpf), is decreased in heterozygous siblings and further decreased in homozygous siblings. In addition, p53 knockdown partially increases otpa levels in the mutant. These data support a model where p53 activation is one of the critical downstream mediators of rps29 knockdown in several tissues, but the mechanism of tissue specificity remains unclear. The otpa phenotype suggests that regulation of some genes is dependent on rps29 levels. The zebrafish rps29 mutant will be a useful model for understanding how a decrease in ribosomal protein levels can cause specific defects in hematopoietic and neural tissues. Disclosures: Zon: FATE, Inc.: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Stemgent: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

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P53 is Activated without RPL11 Upregulation in Diamond-Blackfan Anemia,

Blood ◽

10.1182/blood.v118.21.3432.3432 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3432-3432

Author(s):

Hong-Yan Du ◽

M. Tarek Elghetany ◽

Blanche P Alter ◽

Akiko Shimamura

Keyword(s):

Bone Marrow ◽

Ribosomal Protein ◽

Ribosomal Proteins ◽

Mrna Levels ◽

Protein Levels ◽

Diamond Blackfan Anemia ◽

Human Cd34 ◽

Cd34 Cells ◽

P53 Activation ◽

Ribosomal Stress

Abstract Abstract 3432 Diamond-Blackfan anemia (DBA) is an autosomal dominantly inherited bone marrow failure syndrome characterized by red cell aplasia, physical anomalies, and cancer predisposition. DBA is caused by mutations resulting in haploinsufficiency of genes encoding ribosomal proteins. p53 is activated in the erythroid lineage following reduction of ribosomal protein expression; however the mechanism whereby ribosomal stress results in p53 activation in DBA remains unclear. RPL11 has been proposed to play a central role in p53 activation following ribosomal stress. Reduced expression of individual small ribosomal subunit proteins in a tumor cell line resulted in increased translation of RPL11. Excess free RPL11 can bind and inactivate HDM2, an E3 ubiquitin ligase targeting p53 for degradation. The recent demonstration that cellular responses to ribosomal perturbations vary widely between different tissues raised the question of whether RPL11 upregulation contributes to p53 activation following ribosomal stress in hematopoietic progenitors. To address this question, we modeled DBA in human CD34+ cells. Since RPS19 is the most commonly mutated gene in DBA, we used lentiviral vectors expressing short hairpin RNAs to knock down RPS19 expression in primary human CD34+ cells. RPS19 protein levels were reduced to about 50% of control levels in a manner reflecting the haploinsufficient state in DBA. RPS19 depletion resulted in elevated p53 protein levels and increased mRNA levels of p21, a transcriptional target of p53. Total p53 mRNA levels and p53 mRNA translational activity remained unchanged consistent with a post-transcriptional mechanism for p53 activation. Although total RPL11 mRNA levels were not diminished following RPS19 depletion, RPL11 protein levels were significantly decreased consistent with post-transcriptional downregulation. Depletion of RPS19 in human CD34+ cells did not affect polysome loading of RPL11 mRNA. Reduction of additional ribosomal proteins also accompanied RPS19 knockdown consistent with coordinate regulation of multiple ribosomal protein levels. Corticosteroids, which improve anemia in the majority of DBA patients, did not prevent p53 activation, nor did this improve RPS19 or RPL11 protein levels. Expression of p53 was also assessed in bone marrow biopsy slides from 26 DBA patients with the following genotypes: RPS19 (18), RPS24 (2), RPS26 (2), RPS10 (1), RPS17 (1), RPS7 (1), and RPL11 (1). p53 was over-expressed in all but one patient (RPS26), and was clearly over-expressed in the DBA patient harboring the RPL11 mutation. In summary, we find that p53 activation in DBA does not require upregulation of RPL11 translation or elevated RPL11 protein levels. p53 activation persists in DBA caused by RPL11 deficiency. Corticosteroids do not improve ribosomal protein levels nor do they prevent p53 activation. Disclosures: No relevant conflicts of interest to declare.

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