Patterns of Ribosomal Protein Expression Specify Normal and Malignant Human Cells

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2016 Nov 26

PMID 27884178

Citations 113

Authors

Joao C Guimaraes

Mihaela Zavolan

Affiliations

Soon will be listed here.

Abstract

Background: Ribosomes are highly conserved molecular machines whose core composition has traditionally been regarded as invariant. However, recent studies have reported intriguing differences in the expression of some ribosomal proteins (RPs) across tissues and highly specific effects on the translation of individual mRNAs.

Results: To determine whether RPs are more generally linked to cell identity, we analyze the heterogeneity of RP expression in a large set of human tissues, primary cells, and tumors. We find that about a quarter of human RPs exhibit tissue-specific expression and that primary hematopoietic cells display the most complex patterns of RP expression, likely shaped by context-restricted transcriptional regulators. Strikingly, we uncover patterns of dysregulated expression of individual RPs across cancer types that arise through copy number variations and are predictive for disease progression.

Conclusions: Our study reveals an unanticipated plasticity of RP expression across normal and malignant human cell types and provides a foundation for future characterization of cellular behaviors that are orchestrated by specific RPs.

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References

OLeary M, Schreiber K, Zhang Y, Duc A, Rao S, Hale J . The ribosomal protein Rpl22 controls ribosome composition by directly repressing expression of its own paralog, Rpl22l1. PLoS Genet. 2013; 9(8):e1003708. PMC: 3750023. DOI: 10.1371/journal.pgen.1003708. View

Xue S, Barna M . Specialized ribosomes: a new frontier in gene regulation and organismal biology. Nat Rev Mol Cell Biol. 2012; 13(6):355-69. PMC: 4039366. DOI: 10.1038/nrm3359. View

Wing-Lei Wong Q, Li J, Ng S, Lim S, Yang H, Vardy L . RPL39L is an example of a recently evolved ribosomal protein paralog that shows highly specific tissue expression patterns and is upregulated in ESCs and HCC tumors. RNA Biol. 2014; 11(1):33-41. PMC: 3929422. DOI: 10.4161/rna.27427. View

Ludwig L, Gazda H, Eng J, Eichhorn S, Thiru P, Ghazvinian R . Altered translation of GATA1 in Diamond-Blackfan anemia. Nat Med. 2014; 20(7):748-53. PMC: 4087046. DOI: 10.1038/nm.3557. View

Sandberg R, Neilson J, Sarma A, Sharp P, Burge C . Proliferating cells express mRNAs with shortened 3' untranslated regions and fewer microRNA target sites. Science. 2008; 320(5883):1643-7. PMC: 2587246. DOI: 10.1126/science.1155390. View

Guimaraes J, Rocha M, Arkin A . Transcript level and sequence determinants of protein abundance and noise in Escherichia coli. Nucleic Acids Res. 2014; 42(8):4791-9. PMC: 4005695. DOI: 10.1093/nar/gku126. View

Nadano D, Notsu T, Matsuda T, Sato T . A human gene encoding a protein homologous to ribosomal protein L39 is normally expressed in the testis and derepressed in multiple cancer cells. Biochim Biophys Acta. 2002; 1577(3):430-6. DOI: 10.1016/s0167-4781(02)00445-1. View

Horos R, IJspeert H, Pospisilova D, Sendtner R, Andrieu-Soler C, Taskesen E . Ribosomal deficiencies in Diamond-Blackfan anemia impair translation of transcripts essential for differentiation of murine and human erythroblasts. Blood. 2011; 119(1):262-72. DOI: 10.1182/blood-2011-06-358200. View

Forrest A, Kawaji H, Rehli M, Baillie J, de Hoon M, Haberle V . A promoter-level mammalian expression atlas. Nature. 2014; 507(7493):462-70. PMC: 4529748. DOI: 10.1038/nature13182. View

10.

Thomas G . An encore for ribosome biogenesis in the control of cell proliferation. Nat Cell Biol. 2000; 2(5):E71-2. DOI: 10.1038/35010581. View

11.

Uhlen M, Fagerberg L, Hallstrom B, Lindskog C, Oksvold P, Mardinoglu A . Proteomics. Tissue-based map of the human proteome. Science. 2015; 347(6220):1260419. DOI: 10.1126/science.1260419. View

12.

Gazda H, Grabowska A, Merida-Long L, Latawiec E, Schneider H, Lipton J . Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2006; 79(6):1110-8. PMC: 1698708. DOI: 10.1086/510020. View

13.

Vogel C, de Sousa Abreu R, Ko D, Le S, Shapiro B, Burns S . Sequence signatures and mRNA concentration can explain two-thirds of protein abundance variation in a human cell line. Mol Syst Biol. 2010; 6:400. PMC: 2947365. DOI: 10.1038/msb.2010.59. View

14.

Lohrum M, Ludwig R, Kubbutat M, Hanlon M, Vousden K . Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell. 2003; 3(6):577-87. DOI: 10.1016/s1535-6108(03)00134-x. View

15.

Bee A, Ke Y, Forootan S, Lin K, Beesley C, Forrest S . Ribosomal protein l19 is a prognostic marker for human prostate cancer. Clin Cancer Res. 2006; 12(7 Pt 1):2061-5. DOI: 10.1158/1078-0432.CCR-05-2445. View

16.

Mauro V, Edelman G . The ribosome filter hypothesis. Proc Natl Acad Sci U S A. 2002; 99(19):12031-6. PMC: 129393. DOI: 10.1073/pnas.192442499. View

17.

Henry J, Coggin D, King C . High-level expression of the ribosomal protein L19 in human breast tumors that overexpress erbB-2. Cancer Res. 1993; 53(6):1403-8. View

18.

Orom U, Nielsen F, Lund A . MicroRNA-10a binds the 5'UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell. 2008; 30(4):460-71. DOI: 10.1016/j.molcel.2008.05.001. View

19.

Newman J, Ghaemmaghami S, Ihmels J, Breslow D, Noble M, DeRisi J . Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Nature. 2006; 441(7095):840-6. DOI: 10.1038/nature04785. View

20.

Xiong X, Zhao Y, Tang F, Wei D, Thomas D, Wang X . Ribosomal protein S27-like is a physiological regulator of p53 that suppresses genomic instability and tumorigenesis. Elife. 2014; 3:e02236. PMC: 4163686. DOI: 10.7554/eLife.02236. View