Intron Retention in the Alternatively Spliced Region of RON Results from Weak 3' Splice Site Recognition

PLoS ONE

Volumn 8, Issue 10, 2013, Pages

  Smith, Lindsay D ^a   Lucas, Christian M ^a   Eperon, Ian C ^a  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATE; GLOBIN; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN; ISOPROTEIN; MACROPHAGE STIMULATING PROTEIN; MESSENGER RNA; MESSENGER RNA PRECURSOR; PROTEIN; TYROSINE KINASE RECEPTOR; UNCLASSIFIED DRUG;

ARTICLE; CARCINOMA; CONTROLLED STUDY; CROSS LINKING; EXON; EXON SKIPPING; GENE; GENE EXPRESSION; GENE SEQUENCE; GENETIC TRANSFECTION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INTRON; INTRON RETENTION; INVASIVE CARCINOMA; PROTEIN BINDING; RON GENE; SPLICEOSOME;

ALTERNATIVE SPLICING; BASE SEQUENCE; BETA-GLOBINS; CONSENSUS SEQUENCE; CROSS-LINKING REAGENTS; HELA CELLS; HUMANS; INTRONS; MOLECULAR SEQUENCE DATA; PROTEIN BINDING; RECEPTOR PROTEIN-TYROSINE KINASES; RNA SPLICE SITES; RNA, MESSENGER;

EID: 84885417295     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0077208     Document Type: Article

References (72)

1. Waltz SE, Toms CL, McDowell SA, Clay LA, Muraoka RS, et al. (1998) Characterization of the mouse Ron/Stk receptor tyrosine kinase gene. Oncogene 16: 27-42. doi:10.1038/sj.onc.1201508. PubMed: 9467940.
2. Bezerra JA, Laney DW Jr., Degen SJ, (1994) Increased expression of mRNA for hepatocyte growth factor-like protein during liver regeneration and inflammation. Biochem Biophys Res Commun 203: 666-673. doi:10.1006/bbrc.1994.2234. PubMed: 8074719.
3. Kurihara N, Iwama A, Tatsumi J, Ikeda K, Suda T, (1996) Macrophage-stimulating protein activates STK receptor tyrosine kinase on osteoclasts and facilitates bone resorption by osteoclast-like cells. Blood 87: 3704-3710. PubMed: 8611695.
4. Leonis MA, Toney-Earley K, Degen SJ, Waltz SE, (2002) Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure. Hepatology 36: 1053-1060. doi:10.1053/jhep.2002.36822. PubMed: 12395314.
5. Waltz SE, Eaton L, Toney-Earley K, Hess KA, Peace BE, et al. (2001) Ron-mediated cytoplasmic signaling is dispensable for viability but is required to limit inflammatory responses. J Clin Invest 108: 567-576. doi:10.1172/JCI200111881. PubMed: 11518730.
6. Wang MH, Cox GW, Yoshimura T, Sheffler LA, Skeel A, et al. (1994) Macrophage-stimulating protein inhibits induction of nitric oxide production by endotoxin- or cytokine-stimulated mouse macrophages. J Biol Chem 269: 14027-14031. PubMed: 7514598.
7. Wang MH, Dlugosz AA, Sun Y, Suda T, Skeel A, et al. (1996) Macrophage-stimulating protein induces proliferation and migration of murine keratinocytes. Exp Cell Res 226: 39-46. doi:10.1006/excr.1996.0200. PubMed: 8660937.
8. Lu Y, Yao HP, Wang MH, (2007) Multiple variants of the RON receptor tyrosine kinase: biochemical properties, tumorigenic activities, and potential drug targets. Cancer Lett 257: 157-164. doi:10.1016/j.canlet.2007.08.007. PubMed: 17889431.
9. Camp ER, Liu W, Fan F, Yang A, Somcio R, et al. (2005) RON, a tyrosine kinase receptor involved in tumor progression and metastasis. Ann Surg Oncol 12: 273-281. doi:10.1245/ASO.2005.08.013. PubMed: 15827676.
10. Conrotto P, Corso S, Gamberini S, Comoglio PM, Giordano S, (2004) Interplay between scatter factor receptors and B plexins controls invasive growth. Oncogene 23: 5131-5137. doi:10.1038/sj.onc.1207650. PubMed: 15184888.
11. Thiery JP, Sleeman JP, (2006) Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol 7: 131-142. doi:10.1038/nrm1835. PubMed: 16493418.
12. Trusolino L, Comoglio PM, (2002) Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev Cancer 2: 289-300. doi:10.1038/nrc779. PubMed: 12001990.
13. Wang MH, Wang D, Chen YQ, (2003) Oncogenic and invasive potentials of human macrophage-stimulating protein receptor, the RON receptor tyrosine kinase. Carcinogenesis 24: 1291-1300. doi:10.1093/carcin/bgg089. PubMed: 12807733.
14. Wagh PK, Gray JK, Zinser GM, Vasiliauskas J, James L, et al. (2011) beta-Catenin is required for Ron receptor-induced mammary tumorigenesis. Oncogene 30: 3694-3704. doi:10.1038/onc.2011.86. PubMed: 21423209.
15. Wijnhoven BP, Dinjens WN, Pignatelli M, (2000) E-cadherin-catenin cell-cell adhesion complex and human cancer. Br J Surg 87: 992-1005. doi:10.1046/j.1365-2168.2000.01513.x. PubMed: 10931041.
16. Eckerich C, Schulte A, Martens T, Zapf S, Westphal M, et al. (2009) RON receptor tyrosine kinase in human gliomas: expression, function, and identification of a novel soluble splice variant. J Neurochem 109: 969-980. doi:10.1111/j.1471-4159.2009.06027.x. PubMed: 19519771.
17. Thomas RM, Toney K, Fenoglio-Preiser C, Revelo-Penafiel MP, Hingorani SR, et al. (2007) The RON receptor tyrosine kinase mediates oncogenic phenotypes in pancreatic cancer cells and is increasingly expressed during pancreatic cancer progression. Cancer Res 67: 6075-6082. doi:10.1158/0008-5472.CAN-06-4128. PubMed: 17616662.
18. Zhou D, Pan G, Zheng C, Zheng J, Yian L, et al. (2008) Expression of the RON receptor tyrosine kinase and its association with gastric carcinoma versus normal gastric tissues. BMC Cancer 8: 353. doi:10.1186/1471-2407-8-353. PubMed: 19040718.
19. Ghigna C, Giordano S, Shen HH, Benvenuto F, Castiglioni F, et al. (2005) Cell motility is controlled by SF2/ASF through alternative splicing of the Ron protooncogene. Mol Cell 20: 881-890. doi:10.1016/j.molcel.2005.10.026. PubMed: 16364913.
20. Maggiora P, Lorenzato A, Fracchioli S, Costa B, Castagnaro M, et al. (2003) The RON and MET oncogenes are co-expressed in human ovarian carcinomas and cooperate in activating invasiveness. Exp Cell Res 288: 382-389. doi:10.1016/S0014-4827(03)00250-7. PubMed: 12915129.
21. Chen Q, Seol DW, Carr B, Zarnegar R, (1997) Co-expression and regulation of Met and Ron proto-oncogenes in human hepatocellular carcinoma tissues and cell lines. Hepatology 26: 59-66. doi:10.1002/hep.510260108. PubMed: 9214452.
22. Thobe MN, Gurusamy D, Pathrose P, Waltz SE, (2010) The Ron receptor tyrosine kinase positively regulates angiogenic chemokine production in prostate cancer cells. Oncogene 29: 214-226. doi:10.1038/onc.2009.331. PubMed: 19838218.
23. Cheng HL, Liu HS, Lin YJ, Chen HHW, Hsu PY, et al. (2005) Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder. Br J Cancer 92: 1906-1914. doi:10.1038/sj.bjc.6602593. PubMed: 15870710.
24. Rampino T, Gregorini M, Soccio G, Maggio M, Rosso R, et al. (2003) The Ron proto-oncogene product is a phenotypic marker of renal oncocytoma. Am J Surg Pathol 27: 779-785. doi:10.1097/00000478-200306000-00008. PubMed: 12766581.
25. Collesi C, Santoro MM, Gaudino G, Comoglio PM, (1996) A splicing variant of the RON transcript induces constitutive tyrosine kinase activity and an invasive phenotype. Mol Cell Biol 16: 5518-5526. PubMed: 8816464.
26. Ghigna C, De Toledo M, Bonomi S, Valacca C, Gallo S, et al. (2010) Pro-metastatic splicing of Ron proto-oncogene mRNA can be reversed: Therapeutic potential of bifunctional oligonucleotides and indole derivatives. RNA Biol 7: 495-503. doi:10.4161/rna.7.4.12744. PubMed: 20864806.
27. Wang J, Steinbacher S, Augustin M, Schreiner P, Epstein D, et al. (2010) The crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis. Biochemistry 49: 7972-7974. doi:10.1021/bi100409w. PubMed: 20726546.
28. Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, et al. (2007) The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nat Struct Mol Biol 14: 185-193. doi:10.1038/nsmb1209. PubMed: 17310252.
29. Ghigna C, Valacca C, Biamonti G, (2008) Alternative splicing and tumor progression. Curr Genomics 9: 556-570. doi:10.2174/138920208786847971. PubMed: 19516963.
30. Valacca C, Bonomi S, Buratti E, Pedrotti S, Baralle FE, et al. (2010) Sam68 regulates EMT through alternative splicing-activated nonsense-mediated mRNA decay of the SF2/ASF proto-oncogene. J Cell Biol 191: 87-99. doi:10.1083/jcb.201001073. PubMed: 20876280.
31. Lefave CV, Squatrito M, Vorlova S, Rocco GL, Brennan CW, et al. (2011) Splicing factor hnRNPH drives an oncogenic splicing switch in gliomas. EMBO J 30: 4084-4097. doi:10.1038/emboj.2011.259. PubMed: 21915099.
32. Skordis LA, Dunckley MG, Yue B, Eperon IC, Muntoni F, (2003) Bifunctional antisense oligonucleotides provide a trans-acting splicing enhancer that stimulates SMN2 gene expression in patient fibroblasts. Proc Natl Acad Sci U S A 100: 4114-4119. doi:10.1073/pnas.0633863100. PubMed: 12642665.
33. Hodson MJ, Hudson AJ, Cherny D, Eperon IC, (2012) The transition in spliceosome assembly from complex E to complex A purges surplus U1 snRNPs from alternative splice sites. Nucleic Acids Res 40: 6850-6862. doi:10.1093/nar/gks322. PubMed: 22505580.
34. Cunningham SA, Else AJ, Potter BV, Eperon IC, (1991) Influences of separation and adjacent sequences on the use of alternative 5' splice sites. J Mol Biol 217: 265-281. doi:10.1016/0022-2836(91)90541-D. PubMed: 1825120.
35. Das R, Reed R, (1999) Resolution of the mammalian E complex and the ATP-dependent spliceosomal complexes on native agarose mini-gels. RNA 5: 1504-1508. doi:10.1017/S1355838299991501. PubMed: 10580479.
36. Gama-Carvalho M, Krauss RD, Chiang L, Valcárcel J, Green MR, et al. (1997) Targeting of U2AF65 to Sites of Active Splicing in the Nucleus. J Cell Biol 137: 975-987. doi:10.1083/jcb.137.5.975. PubMed: 9166400.
37. Wieringa B, Hofer E, Weissmann C, (1984) A minimal intron length but no specific internal sequence is required for splicing the large rabbit beta-globin intron. Cell 37: 915-925. doi:10.1016/0092-8674(84)90426-4. PubMed: 6204770.
38. Yue Y, Bai-Gong, Akusjärvi G (1999) A downstream splicing enhancer is essential for in vitro pre-mRNA splicing. FEBS Lett 451: 10-14. doi:10.1016/S0014-5793(99)00521-9. PubMed: 10356974.
39. Das R, Dufu K, Romney B, Feldt M, Elenko M, et al. (2006) Functional coupling of RNAP II transcription to spliceosome assembly. Genes Dev 20: 1100-1109. doi:10.1101/gad.1397406. PubMed: 16651655.
40. Jamison SF, Garcia-Blanco MA, (1992) An ATP-independent U2 small nuclear ribonucleoprotein particle/precursor mRNA complex requires both splice sites and the polypyrimidine tract. Proc Natl Acad Sci U S A 89: 5482-5486. doi:10.1073/pnas.89.12.5482. PubMed: 1535158.
41. Makarov EM, Owen N, Bottrill A, Makarova OV, (2012) Functional mammalian spliceosomal complex E contains SMN complex proteins in addition to U1 and U2 snRNPs. Nucleic Acids Res 40: 2639-2652. doi:10.1093/nar/gkr1056. PubMed: 22110043.
42. Michaud S, Reed R, (1991) An ATP-independent complex commits pre-mRNA to the mammalian spliceosome assembly pathway. Genes Dev 5: 2534-2546. doi:10.1101/gad.5.12b.2534. PubMed: 1836445.
43. Michaud S, Reed R, (1993) A functional association between the 5' and 3' splice site is established in the earliest prespliceosome complex (E) in mammals. Genes Dev 7: 1008-1020. doi:10.1101/gad.7.6.1008. PubMed: 8504926.
44. Caputi M, Zahler AM, (2001) Determination of the RNA binding specificity of the heterogeneous nuclear ribonucleoprotein (hnRNP) H/H'/F/2H9 family. J Biol Chem 276: 43850-43859. doi:10.1074/jbc.M102861200. PubMed: 11571276.
45. Dominguez C, Fisette JF, Chabot B, Allain FH, (2010) Structural basis of G-tract recognition and encaging by hnRNP F quasi-RRMs. Nat Struct Mol Biol 17: 853-861. doi:10.1038/nsmb.1814. PubMed: 20526337.
46. Kafasla P, Mickleburgh I, Llorian M, Coelho M, Gooding C, et al. (2012) Defining the roles and interactions of PTB. Biochem Soc Trans 40: 815-820. doi:10.1042/BST20120044. PubMed: 22817740.
47. Zamore PD, Patton JG, Green MR, (1992) Cloning and domain structure of the mammalian splicing factor U2AF. Nature 355: 609-614. doi:10.1038/355609a0. PubMed: 1538748.
48. Zarnack K, König J, Tajnik M, Martincorena I, Eustermann S, et al. (2013) Direct competition between hnRNP C and U2AF65 protects the transcriptome from the exonization of Alu elements. Cell 152: 453-466. doi:10.1016/j.cell.2012.12.023. PubMed: 23374342.
49. Cherny D, Gooding C, Eperon GE, Coelho MB, Bagshaw CR, et al. (2010) Stoichiometry of a regulatory splicing complex revealed by single-molecule analyses. EMBO J 29: 2161-2172. doi:10.1038/emboj.2010.103. PubMed: 20502437.
50. Berglund JA, Abovich N, Rosbash M, (1998) A cooperative interaction between U2AF65 and mBBP/SF1 facilitates branchpoint region recognition. Genes Dev 12: 858-867. doi:10.1101/gad.12.6.858. PubMed: 9512519.
51. Huang T, Vilardell J, Query CC, (2002) Pre-spliceosome formation in S.pombe requires a stable complex of SF1-U2AF(59)-U2AF. EMBO JVolumes 23: 21: 5516-5526.
52. Peled-Zehavi H, Berglund JA, Rosbash M, Frankel AD, (2001) Recognition of RNA branch point sequences by the KH domain of splicing factor 1 (mammalian branch point binding protein) in a splicing factor complex. Mol Cell Biol 21: 5232-5241. doi:10.1128/MCB.21.15.5232-5241.2001. PubMed: 11438677.
53. Gama-Carvalho M, Barbosa-Morais NL, Brodsky AS, Silver PA, Carmo-Fonseca M, (2006) Genome-wide identification of functionally distinct subsets of cellular mRNAs associated with two nucleocytoplasmic-shuttling mammalian splicing factors. Genome Biol 7: R113. doi:10.1186/gb-2006-7-8-113. PubMed: 17137510.
54. Tavanez JP, Madl T, Kooshapur H, Sattler M, Valcárcel J, (2012) hnRNP A1 proofreads 3' splice site recognition by U2AF. Mol Cell 45: 314-329. doi:10.1016/j.molcel.2011.11.033. PubMed: 22325350.
55. Corrionero A, Raker VA, Izquierdo JM, Valcárcel J, (2011) Strict 3' splice site sequence requirements for U2 snRNP recruitment after U2AF binding underlie a genetic defect leading to autoimmune disease. RNA 17: 401-411. doi:10.1261/rna.2444811. PubMed: 21233219.
56. Lefévre SH, Chauveinc L, Stoppa-Lyonnet D, Michon J, Lumbroso L, et al. (2002) A T to C mutation in the polypyrimidine tract of the exon 9 splicing site of the RB1 gene responsible for low penetrance hereditary retinoblastoma. J Med Genet 39: E21. doi:10.1136/jmg.39.5.e21. PubMed: 12011162.
57. Lim SR, Hertel KJ, (2001) Modulation of survival motor neuron pre-mRNA splicing by inhibition of alternative 3' splice site pairing. J Biol Chem 276: 45476-45483. doi:10.1074/jbc.M107632200. PubMed: 11584013.
58. Martins de Araújo M, Bonnal S, Hastings ML, Krainer AR, Valcárcel J, (2009) Differential 3' splice site recognition of SMN1 and SMN2 transcripts by U2AF and U2 snRNP. RNA 15: 515-523. doi:10.1261/rna.1273209. PubMed: 19244360.
59. Kent OA, Ritchie DB, Macmillan AM, (2005) Characterization of a U2AF-independent commitment complex (E') in the mammalian spliceosome assembly pathway. Mol Cell Biol 25: 233-240. doi:10.1128/MCB.25.1.233-240.2005. PubMed: 15601845.
60. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, et al. (2001) Initial sequencing and analysis of the human genome. Nature 409: 860-921. doi:10.1038/35057062. PubMed: 11237011.
61. Wang D, Yu J, (2011) Both Size and GC-Content of Minimal Introns Are Selected in Human Populations. PLOS ONE 6: e17945. doi:10.1371/journal.pone.0017945. PubMed: 21437290.
62. Amit M, Donyo M, Hollander D, Goren A, Kim E, et al. (2012) Differential GC Content between Exons and Introns Establishes Distinct Strategies of Splice-Site Recognition. Cell Rep 1: 543-556. doi:10.1016/j.celrep.2012.03.013. PubMed: 22832277.
63. Fox-Walsh KL, Dou Y, Lam BJ, Hung SP, Baldi PF, et al. (2005) The architecture of pre-mRNAs affects mechanisms of splice-site pairing. Proc Natl Acad Sci U S A 102: 16176-16181. doi:10.1073/pnas.0508489102. PubMed: 16260721.
64. Hertel KJ, (2008) Combinatorial control of exon recognition. J Biol Chem 283: 1211-1215. PubMed: 18024426.
65. Pandit S, Wang D, Fu XD, (2008) Functional integration of transcriptional and RNA processing machineries. Curr Opin Cell Biol 20: 260-265. doi:10.1016/j.ceb.2008.03.001. PubMed: 18436438.
66. Shukla S, Oberdoerffer S, (2012) Co-transcriptional regulation of alternative pre-mRNA splicing. Biochim Biophys Acta 1819: 673-683. doi:10.1016/j.bbagrm.2012.01.014. PubMed: 22326677.
67. Eperon LP, Graham IR, Griffiths AD, Eperon IC, (1988) Effects of RNA secondary structure on alternative splicing of pre-mRNA: is folding limited to a region behind the transcribing RNA polymerase? Cell 54: 393-401. doi:10.1016/0092-8674(88)90202-4. PubMed: 2840206.
68. Samatanga B, Dominguez C, Jelesarov I, Allain FH, (2013) The high kinetic stability of a G-quadruplex limits hnRNP F qRRM3 binding to G-tract RNA. Nucleic Acids Res 41: 2505-2516. doi:10.1093/nar/gks1289. PubMed: 23275549.
69. Chen CD, Kobayashi R, Helfman DM, (1999) Binding of hnRNP H to an exonic splicing silencer is involved in the regulation of alternative splicing of the rat beta-tropomyosin gene. Genes Dev 13: 593-606. doi:10.1101/gad.13.5.593. PubMed: 10072387.
70. Lane AN, Chaires JB, Gray RD, Trent JO, (2008) Stability and kinetics of G-quadruplex structures. Nucleic Acids Res 36: 5482-5515. doi:10.1093/nar/gkn517. PubMed: 18718931.
71. Mergny JL, De Cian A, Ghelab A, Saccà B, Lacroix L, (2005) Kinetics of tetramolecular quadruplexes. Nucleic Acids Res 33: 81-94. doi:10.1093/nar/gni080. PubMed: 15642696.
72. Ortuño-Pineda C, Galindo-Rosales JM, Calderón-Salinas JV, Villegas-Sepúlveda N, Saucedo-Cárdenas O, et al. (2012) Binding of hnRNP H and U2AF65 to respective G-codes and a poly-uridine tract collaborate in the N50-5'ss selection of the REST N exon in H69 cells. PLOS ONE 7: e40315. doi:10.1371/journal.pone.0040315. PubMed: 22792276.