Ribosomal Proteins RPS11 and RPS20, Two Stress-Response Markers of Glioblastoma Stem Cells, Are Novel Predictors of Poor Prognosis in Glioblastoma Patients

Yong, William H.; Shabihkhani, Maryam; Telesca, Donatello; Yang, Shuai; Tso, Jonathan L.; Menjivar, Jimmy C.; Wei, Bowen; Lucey, Gregory M.; Mareninov, Sergey; Chen, Zugen; Liau, Linda M.; Lai, Albert; Nelson, Stanley F.; Cloughesy, Timothy F.; Tso, Cho-Lea

doi:10.1371/journal.pone.0141334

Cited by 58 publications

(42 citation statements)

References 63 publications

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“…One of the few canonical RPs we found to be differentially incorporated was RpS11 in the head 80S ribosomes. RpS11 phosphorylation, in humans, has been found to be linked to Parkinson’s disease [39] and higher levels of RpS11 correlate with poorer prognosis in glioblastoma patients [40]. Therefore, understanding RpS11 levels in Drosophila head could provide a mechanism of future exploration for dissecting the molecular mechanisms by which RP mutations result in human disease.…”

Section: Discussionmentioning

confidence: 99%

Ribosome heterogeneity in Drosophila melanogaster gonads through paralog-switching

Aspden

Fontana

O’Connell

et al. 2020

Preprint

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13Ribosomes have long been thought of as homogeneous, macromolecular machines but 14 recent evidence suggests they are heterogeneous and their specialisation can regulate translation. 15Here, we have characterised ribosomal protein heterogeneity across 5 tissues of Drosophila 16 melanogaster. We find that testis and ovary contain the most heterogeneous ribosome populations, 17 and that specialisation in these tissues occurs through paralog-switching. For the first time, we have 18 solved structures of ribosomes purified from in vivo tissues by cryo-EM, revealing differences in 19 precise ribosomal arrangement for testis and ovary 80S ribosomes. Differences in the amino acid 20 composition of paralog pairs and their localisation on the ribosome exterior indicate paralog-21 switching could alter the ribosome surface, enabling different proteins to regulate translation. One 22 testis-specific paralog-switching pair is also found in humans, suggesting this is a conserved site of 23 ribosome specialisation. Overall, this work allows us to propose possible mechanisms by which 24 ribosome specialisation can regulate translation. 25 26 27 48 effects [1], whilst RpL38 mutants in D. melanogaster exhibit large wings, small bristles, delayed 49 development and disorganised wing hair polarity [14]. 50 2 Human cytoplasmic ribosomes usually comprise of 80 RPs and 4 rRNAs. This is similar across 51 the majority of multicellular eukaryotes including D. melanogaster with 80 RPs and 5 rRNAs. 52 However, annotated in FlyBase there are 93 cytoplasmic RP genes, including 39 small subunit 53 proteins and 54 large subunit proteins [15]. These additional genes code for 13 paralogs in D. 54 melanogaster. In fact, across eukaryotes many RP genes possess paralogs, for example human RpL3 55 and RpL3L [11] and Arabidopsis RpS8A and RpS8B [13]. In total, there are 19 pairs of paralogs in 56 humans [4] and all 80 RPs in Arabidopsis thaliana have paralogs [16].57 To dissect the function of ribosome heterogeneity it is necessary to understand biological 58 importance within context of whole organisms. Within the developmental biology field, a large 59 proportion of research focuses on the contribution of transcription to gene expression control.60 However, during development a variety of processes and key time points are highly dependent on 61 the regulation of mRNA translation (oogenesis in Xenopus [17], early embryo development in 62 Drosophila [18] and mammalian erythropoiesis [19]). The balance between self-renewal and 63 differentiation at the stem cell niche is highly dependent on translation in both the ovary and the 64 testis [20]. This is exemplified by disruptions to the stem cell niche in the testis when RPs are 65 knocked down e.g. RpL19 RNAi results in over-proliferation of early germ cells in D. melanogaster 66 [21]. During the meiotic phase of gametogenesis, transcription does not occur [22]; therefore 67 meiotic cells rely on post-transcriptional gene regulation [23]. The translational machinery has 68 evolved to become specialise...

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Section: Discussionmentioning

confidence: 99%

Ribosome heterogeneity in Drosophila melanogaster gonads through paralog-switching

Aspden

Fontana

O’Connell

et al. 2020

Preprint

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“…(Tian et al, 2015) Glioblastoma S11, S15a, S20 Upregulation Overexpression of S11 and S20 is associated with shorter patient survival. (Yao et al, 2015;Yong et al, 2015) Pancreatic cancer L15 Downregulation Low expression of L15 is associated with tumor progression and predicts poor overall survival. (Yan et al, 2015) Ovarian cancer L13a, L29 Upregulation Low level of S4X in human serous epithelial ovarian cancer is associated with poor prognosis.…”

Section: Rps As Potential Cancer Biomarkersmentioning

confidence: 99%

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity

Xiong

Sun

2016

Sci. China Life Sci.

103

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Ribosomal proteins (RPs), the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have additional extra-ribosomal functions, independent of protein biosynthesis, in regulation of diverse cellular processes. Here, we review recent advances in our understanding of how RPs regulate apoptosis, cell cycle arrest, cell proliferation, neoplastic transformation, cell migration and invasion, and tumorigenesis through both MDM2/p53-dependent and p53-independent mechanisms. We also discuss the roles of RPs in the maintenance of genome integrity via modulating DNA damage response and repair. We further discuss mutations or deletions at the somatic or germline levels of some RPs in human cancers as well as in patients of Diamond-Blackfan anemia and 5q-syndrome with high susceptibility to cancer development. Moreover, we discuss the potential clinical application, based upon abnormal levels of RPs, in biomarker development for early diagnosis and/or prognosis of certain human cancers. Finally, we discuss the pressing issues in the field as future perspectives for better understanding the roles of RPs in human cancers to eventually benefit human health. ribosomal protein, tumorigenesis, genomic integrity, ribosomal stress, p53, MDM2 Citation:Xu, X., Xiong, X., and Sun, Y. (2016). The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity. Sci China Life Sci 59, 656 -672.

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“…Of these GO terms, ribosomal, RNA, and ubiquitin related are among the pathways holding the highest statistical significance. Ribosomal proteins are most commonly known to be involved in protein synthesis but have also been shown to exert extraribosomal functions including immune signaling and development of various cell types as well as being implicated in various cancers including glioblastoma, gastrointestinal, prostate, and lung . In this study, expression levels of many genes, encoding ribosomal proteins (Rp), were found to be differentially regulated in both Tpm1.12‐ and Tpm2.1‐overexpressing cells including Rpl9, Rpl13, Rpl19, and Rpl22 .…”

Section: Resultsmentioning

confidence: 77%

Tropomyosin isoforms have specific effects on the transcriptome of undifferentiated and differentiated B35 neuroblastoma cells

et al. 2018

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Tropomyosins, a family of actin‐associated proteins, bestow actin filaments with distinct biochemical and physical properties which are important for determining cell shape and regulating many cellular processes in eukaryotic cells. Here, we used RNA‐seq to investigate the effect of four tropomyosin isoforms on gene expression in undifferentiated and differentiated rat B35 neuroblastoma cells. In undifferentiated cells, overexpression of tropomyosin isoforms Tpm1.12, Tpm2.1, Tpm3.1, and Tpm4.2 differentially regulates a vast number of genes, clustering into several gene ontology terms. In differentiated cells, tropomyosin overexpression exerts a much weaker influence on overall gene expression. Our findings are particularly compelling because they demonstrate that tropomyosin‐dependent changes are attenuated once the cells are induced to follow a defined path of differentiation. Database Sequence data for public availability are deposited in the European Nucleotide Archive under the accession number PRJEB24136.

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Ribosomal Proteins RPS11 and RPS20, Two Stress-Response Markers of Glioblastoma Stem Cells, Are Novel Predictors of Poor Prognosis in Glioblastoma Patients

Cited by 58 publications

References 63 publications

Ribosome heterogeneity in Drosophila melanogaster gonads through paralog-switching

Ribosome heterogeneity in Drosophila melanogaster gonads through paralog-switching

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity

Tropomyosin isoforms have specific effects on the transcriptome of undifferentiated and differentiated B35 neuroblastoma cells

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