Emerging roles of RNA and RNA-binding protein network in cancer cells.

Recent advances in RNA biology reveal unexpected diversity and complexity of cellular RNA metabolism. RNA-binding proteins (RBPs) are essential players in RNA metabolism, regulating RNA splicing, transport, surveillance, decay and translation. Aberrant expression of RBPs affects many steps of RNA metabolism, significantly altering expression of RNA. Thus, altered expression and dysfuncting of RBPs are implicated in the development of various diseases including cancer. In this minireview, we briefly describe emerging roles of RBPs as a global coordinator of post-transcriptional steps and altered RBP as a global generator of cancer related RNA alternative splicing. Identification and characterization of the RNA-RBP network would expand the scope of cellular RNA metabolism and provide novel anti-cancer therapeutic targets based on cancer specific RNA-RBP interaction.

[1]  T. Glisovic,et al.  RNA‐binding proteins and post‐transcriptional gene regulation , 2008, FEBS letters.

[2]  Gil Ast,et al.  Insights into the connection between cancer and alternative splicing. , 2008, Trends in genetics : TIG.

[3]  C. Sette,et al.  The RNA-binding protein Sam68 contributes to proliferation and survival of human prostate cancer cells , 2007, Oncogene.

[4]  Chunxu Qu,et al.  EWS/FLI-1 Induces Rapid Onset of Myeloid/Erythroid Leukemia in Mice , 2007, Molecular and Cellular Biology.

[5]  D. D. de Rooij,et al.  Male sterility and enhanced radiation sensitivity in TLS−/− mice , 2000, The EMBO journal.

[6]  P. Brown,et al.  Extensive Association of Functionally and Cytotopically Related mRNAs with Puf Family RNA-Binding Proteins in Yeast , 2004, PLoS biology.

[7]  M. Pajares,et al.  Alternative splicing: an emerging topic in molecular and clinical oncology. , 2007, The Lancet. Oncology.

[8]  Gabriele Varani,et al.  RNA is rarely at a loss for companions; as soon as RNA , 2008 .

[9]  Daniel Herschlag,et al.  Diverse RNA-Binding Proteins Interact with Functionally Related Sets of RNAs, Suggesting an Extensive Regulatory System , 2008, PLoS biology.

[10]  R. Chiquet‐Ehrismann,et al.  Tenascin-C induced signaling in cancer. , 2006, Cancer letters.

[11]  N. Ferrara,et al.  The biology of VEGF and its receptors , 2003, Nature Medicine.

[12]  Gil Ast,et al.  Alternative splicing and disease , 2008, RNA biology.

[13]  Sunjoo Jeong,et al.  β-Catenin stabilizes Cyclooxygenase-2 mRNA by interacting with AU-rich elements of 3′-UTR , 2006, Nucleic acids research.

[14]  R. Malik,et al.  RNA regulation and cancer development. , 2007, Cancer letters.

[15]  A. Krainer,et al.  The gene encoding the splicing factor SF2/ASF is a proto-oncogene , 2007, Nature Structural &Molecular Biology.

[16]  T. Maniatis,et al.  An extensive network of coupling among gene expression machines , 2002, Nature.

[17]  Kai-Wei Chang,et al.  RNA-binding proteins in human genetic disease. , 2008, Trends in genetics : TIG.

[18]  J. Keene.  RNA regulons: coordination of post-transcriptional events , 2007, Nature Reviews Genetics.

[19]  J. Ule,et al.  Evolution of Nova-Dependent Splicing Regulation in the Brain , 2007, PLoS genetics.

[20]  J. L. Jennings,et al.  Systematic identification and functional screens of uncharacterized proteins associated with eukaryotic ribosomal complexes. , 2006, Genes & development.

[21]  J. Steitz,et al.  SRprises along a messenger's journey. , 2005, Molecular cell.

[22]  P. Herrlich,et al.  Signal-dependent regulation of splicing via phosphorylation of Sam68 , 2002, Nature.

[23]  Britta Hartmann,et al.  Genome-wide Analysis of Alternative Pre-mRNA Splicing* , 2008, Journal of Biological Chemistry.

[24]  Stefan Stamm,et al.  Regulation of Alternative Splicing by Reversible Protein Phosphorylation* , 2008, Journal of Biological Chemistry.

[25]  Xin Wang,et al.  Identification of Nuclear and Cytoplasmic mRNA Targets for the Shuttling Protein SF2/ASF , 2008, PloS one.

[26]  G. Orphanides,et al.  A Unified Theory of Gene Expression , 2002, Cell.

[27]  Lili Wan,et al.  RNA and Disease , 2009, Cell.

[28]  J. Venables.  Aberrant and Alternative Splicing in Cancer , 2004, Cancer Research.

[29]  A. Krainer,et al.  The splicing-factor oncoprotein SF2/ASF activates mTORC1 , 2008, Proceedings of the National Academy of Sciences.

[30]  P. Walter,et al.  Gene Recruitment of the Activated INO1 Locus to the Nuclear Membrane , 2004, PLoS biology.

[31]  N. Gray,et al.  A novel role for shuttling SR proteins in mRNA translation. , 2004, Genes & development.

[32]  Guey-Shin Wang,et al.  Splicing in disease: disruption of the splicing code and the decoding machinery , 2007, Nature Reviews Genetics.

[33]  A. Hinnebusch,et al.  New modes of translational control in development, behavior, and disease. , 2007, Molecular cell.

[34]  S. Nedvetzki,et al.  CD44 in Cancer , 2002, Critical reviews in clinical laboratory sciences.

[35]  Phillip A Sharp,et al.  The Centrality of RNA , 2009, Cell.

[36]  F. Kittrell,et al.  Stage-specific changes in SR splicing factors and alternative splicing in mammary tumorigenesis , 1999, Oncogene.

[37]  A. Goffeau,et al.  Compensatory activation of the multidrug transporters Pdr5p, Snq2p, and Yor1p by Pdr1p in Saccharomyces cerevisiae , 2008, FEBS letters.

[38]  K. Lukong,et al.  Sam68, the KH domain-containing superSTAR. , 2003, Biochimica et biophysica acta.

[39]  Tyson A. Clark,et al.  HITS-CLIP yields genome-wide insights into brain alternative RNA processing , 2008, Nature.

[40]  S. Stamm,et al.  Function of Alternative Splicing , 2004 .

[41]  Jung Hur,et al.  beta-catenin regulates multiple steps of RNA metabolism as revealed by the RNA aptamer in colon cancer cells. , 2007, Cancer research.

[42]  K. J. Hertel,et al.  Combinatorial Control of Exon Recognition* , 2008, Journal of Biological Chemistry.

[43]  Nicolò Riggi,et al.  Sarcomas: genetics, signalling, and cellular origins. Part 1: The fellowship of TET , 2007, The Journal of pathology.

[44]  Melissa J. Moore,et al.  Pre-mRNA Processing Reaches Back toTranscription and Ahead to Translation , 2009, Cell.

[45]  K. Lynch,et al.  Regulation of Alternative Splicing: More than Just the ABCs* , 2008, Journal of Biological Chemistry.

[46]  Christopher J. Lee,et al.  Discovery of novel splice forms and functional analysis of cancer-specific alternative splicing in human expressed sequences. , 2003, Nucleic acids research.

[47]  J. Cáceres,et al.  The splicing factor SF2/ASF regulates translation initiation by enhancing phosphorylation of 4E-BP1. , 2008, Molecular cell.

[48]  T. Cech,et al.  Crawling Out of the RNA World , 2009, Cell.

[49]  D. Cazalla,et al.  Reversible phosphorylation differentially affects nuclear and cytoplasmic functions of splicing factor 2/alternative splicing factor. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[50]  R. Johnson,et al.  Isoforms of Vascular Endothelial Growth Factor Act in a Coordinate Fashion To Recruit and Expand Tumor Vasculature , 2000, Molecular and Cellular Biology.

[51]  Y. Audic,et al.  Post‐transcriptional regulation in cancer , 2004, Biology of the cell.

[52]  M. Fedor.  Alternative Splicing Minireview Series: Combinatorial Control Facilitates Splicing Regulation of Gene Expression and Enhances Genome Diversity* , 2008, Journal of Biological Chemistry.

[53]  R. Zimmer,et al.  Alternative splicing and protein structure evolution. , 2008, Nucleic acids research.

[54]  J. Richardson,et al.  Expression of the EWS/FLI-1 oncogene in murine primary bone-derived cells Results in EWS/FLI-1-dependent, ewing sarcoma-like tumors. , 2005, Cancer research.

[55]  W. Watford,et al.  Ewing sarcoma gene EWS is essential for meiosis and B lymphocyte development. , 2007, The Journal of clinical investigation.