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. 1996 Feb 1;24(3):478–485. doi: 10.1093/nar/24.3.478

The neurofibromatosis type I messenger RNA undergoes base-modification RNA editing.

G R Skuse 1, A J Cappione 1, M Sowden 1, L J Metheny 1, H C Smith 1
PMCID: PMC145654  PMID: 8602361

Abstract

A functional mooring sequence, known to be required for apolipoprotein B (apoB) mRNA editing, exists in the mRNA encoding the neurofibromatosis type I (NF1) tumor suppressor. Editing of NF1 mRNA modifies cytidine in an arginine codon (CGA) at nucleotide 2914 to a uridine (UGA), creating an in frame translation stop codon. NF1 editing occurs in normal tissue but was several-fold higher in tumors. In vitro editing and transfection assays demonstrated that apoB and NF1 RNA editing will take place in both neural tumor and hepatoma cells. Unlike apoB, NF1 editing did not demonstrate dependence on rate-limiting quantities of APOBEC-1 (the apoB editing catalytic subunit) suggesting that different trans-acting factors may be involved in the two editing processes.

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Selected References

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  1. Anant S., MacGinnitie A. J., Davidson N. O. apobec-1, the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme, is a novel RNA-binding protein. J Biol Chem. 1995 Jun 16;270(24):14762–14767. [PubMed] [Google Scholar]
  2. Backus J. W., Schock D., Smith H. C. Only cytidines 5' of the apolipoprotein B mRNA mooring sequence are edited. Biochim Biophys Acta. 1994 Sep 13;1219(1):1–14. doi: 10.1016/0167-4781(94)90240-2. [DOI] [PubMed] [Google Scholar]
  3. Backus J. W., Smith H. C. Apolipoprotein B mRNA sequences 3' of the editing site are necessary and sufficient for editing and editosome assembly. Nucleic Acids Res. 1991 Dec 25;19(24):6781–6786. doi: 10.1093/nar/19.24.6781. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Backus J. W., Smith H. C. Specific 3' sequences flanking a minimal apolipoprotein B (apoB) mRNA editing 'cassette' are critical for efficient editing in vitro. Biochim Biophys Acta. 1994 Jan 18;1217(1):65–73. [PubMed] [Google Scholar]
  5. Backus J. W., Smith H. C. Three distinct RNA sequence elements are required for efficient apolipoprotein B (apoB) RNA editing in vitro. Nucleic Acids Res. 1992 Nov 25;20(22):6007–6014. doi: 10.1093/nar/20.22.6007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ballester R., Marchuk D., Boguski M., Saulino A., Letcher R., Wigler M., Collins F. The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins. Cell. 1990 Nov 16;63(4):851–859. doi: 10.1016/0092-8674(90)90151-4. [DOI] [PubMed] [Google Scholar]
  7. Beier H., Lee M. C., Sekiya T., Kuchino Y., Nishimura S. Two nucleotides next to the anticodon of cytoplasmic rat tRNA(Asp) are likely generated by RNA editing. Nucleic Acids Res. 1992 Jun 11;20(11):2679–2683. doi: 10.1093/nar/20.11.2679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Belgrader P., Cheng J., Zhou X., Stephenson L. S., Maquat L. E. Mammalian nonsense codons can be cis effectors of nuclear mRNA half-life. Mol Cell Biol. 1994 Dec;14(12):8219–8228. doi: 10.1128/mcb.14.12.8219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Belgrader P., Maquat L. E. Nonsense but not missense mutations can decrease the abundance of nuclear mRNA for the mouse major urinary protein, while both types of mutations can facilitate exon skipping. Mol Cell Biol. 1994 Sep;14(9):6326–6336. doi: 10.1128/mcb.14.9.6326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Boström K., Lauer S. J., Poksay K. S., Garcia Z., Taylor J. M., Innerarity T. L. Apolipoprotein B48 RNA editing in chimeric apolipoprotein EB mRNA. J Biol Chem. 1989 Sep 15;264(26):15701–15708. [PubMed] [Google Scholar]
  11. Buchberg A. M., Cleveland L. S., Jenkins N. A., Copeland N. G. Sequence homology shared by neurofibromatosis type-1 gene and IRA-1 and IRA-2 negative regulators of the RAS cyclic AMP pathway. Nature. 1990 Sep 20;347(6290):291–294. doi: 10.1038/347291a0. [DOI] [PubMed] [Google Scholar]
  12. Chen C. A., Okayama H. Calcium phosphate-mediated gene transfer: a highly efficient transfection system for stably transforming cells with plasmid DNA. Biotechniques. 1988 Jul-Aug;6(7):632–638. [PubMed] [Google Scholar]
  13. Chen S. H., Habib G., Yang C. Y., Gu Z. W., Lee B. R., Weng S. A., Silberman S. R., Cai S. J., Deslypere J. P., Rosseneu M. Apolipoprotein B-48 is the product of a messenger RNA with an organ-specific in-frame stop codon. Science. 1987 Oct 16;238(4825):363–366. doi: 10.1126/science.3659919. [DOI] [PubMed] [Google Scholar]
  14. Cheng J., Maquat L. E. Nonsense codons can reduce the abundance of nuclear mRNA without affecting the abundance of pre-mRNA or the half-life of cytoplasmic mRNA. Mol Cell Biol. 1993 Mar;13(3):1892–1902. doi: 10.1128/mcb.13.3.1892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  16. Davidson N. O., Innerarity T. L., Scott J., Smith H., Driscoll D. M., Teng B., Chan L. Proposed nomenclature for the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme: APOBEC-1. RNA. 1995 Mar;1(1):3–3. [PMC free article] [PubMed] [Google Scholar]
  17. Davidson N. O., Powell L. M., Wallis S. C., Scott J. Thyroid hormone modulates the introduction of a stop codon in rat liver apolipoprotein B messenger RNA. J Biol Chem. 1988 Sep 25;263(27):13482–13485. [PubMed] [Google Scholar]
  18. Davies M. S., Wallis S. C., Driscoll D. M., Wynne J. K., Williams G. W., Powell L. M., Scott J. Sequence requirements for apolipoprotein B RNA editing in transfected rat hepatoma cells. J Biol Chem. 1989 Aug 15;264(23):13395–13398. [PubMed] [Google Scholar]
  19. Dietz H. C., Valle D., Francomano C. A., Kendzior R. J., Jr, Pyeritz R. E., Cutting G. R. The skipping of constitutive exons in vivo induced by nonsense mutations. Science. 1993 Jan 29;259(5095):680–683. doi: 10.1126/science.8430317. [DOI] [PubMed] [Google Scholar]
  20. Driscoll D. M., Lakhe-Reddy S., Oleksa L. M., Martinez D. Induction of RNA editing at heterologous sites by sequences in apolipoprotein B mRNA. Mol Cell Biol. 1993 Dec;13(12):7288–7294. doi: 10.1128/mcb.13.12.7288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Driscoll D. M., Zhang Q. Expression and characterization of p27, the catalytic subunit of the apolipoprotein B mRNA editing enzyme. J Biol Chem. 1994 Aug 5;269(31):19843–19847. [PubMed] [Google Scholar]
  22. Easton D. F., Ponder M. A., Huson S. M., Ponder B. A. An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): evidence for modifying genes. Am J Hum Genet. 1993 Aug;53(2):305–313. [PMC free article] [PubMed] [Google Scholar]
  23. Egebjerg J., Kukekov V., Heinemann S. F. Intron sequence directs RNA editing of the glutamate receptor subunit GluR2 coding sequence. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10270–10274. doi: 10.1073/pnas.91.22.10270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Giannoni F., Bonen D. K., Funahashi T., Hadjiagapiou C., Burant C. F., Davidson N. O. Complementation of apolipoprotein B mRNA editing by human liver accompanied by secretion of apolipoprotein B48. J Biol Chem. 1994 Feb 25;269(8):5932–5936. [PubMed] [Google Scholar]
  25. Harris S. G., Sabio I., Mayer E., Steinberg M. F., Backus J. W., Sparks J. D., Sparks C. E., Smith H. C. Extract-specific heterogeneity in high-order complexes containing apolipoprotein B mRNA editing activity and RNA-binding proteins. J Biol Chem. 1993 Apr 5;268(10):7382–7392. [PubMed] [Google Scholar]
  26. Herrick D. J., Ross J. The half-life of c-myc mRNA in growing and serum-stimulated cells: influence of the coding and 3' untranslated regions and role of ribosome translocation. Mol Cell Biol. 1994 Mar;14(3):2119–2128. doi: 10.1128/mcb.14.3.2119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Higuchi K., Kitagawa K., Kogishi K., Takeda T. Developmental and age-related changes in apolipoprotein B mRNA editing in mice. J Lipid Res. 1992 Dec;33(12):1753–1764. [PubMed] [Google Scholar]
  28. Higuchi M., Single F. N., Köhler M., Sommer B., Sprengel R., Seeburg P. H. RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency. Cell. 1993 Dec 31;75(7):1361–1370. doi: 10.1016/0092-8674(93)90622-w. [DOI] [PubMed] [Google Scholar]
  29. Huson S. M., Compston D. A., Clark P., Harper P. S. A genetic study of von Recklinghausen neurofibromatosis in south east Wales. I. Prevalence, fitness, mutation rate, and effect of parental transmission on severity. J Med Genet. 1989 Nov;26(11):704–711. doi: 10.1136/jmg.26.11.704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Inui Y., Giannoni F., Funahashi T., Davidson N. O. REPR and complementation factor(s) interact to modulate rat apolipoprotein B mRNA editing in response to alterations in cellular cholesterol flux. J Lipid Res. 1994 Aug;35(8):1477–1489. [PubMed] [Google Scholar]
  31. Janke A., Päbo S. Editing of a tRNA anticodon in marsupial mitochondria changes its codon recognition. Nucleic Acids Res. 1993 Apr 11;21(7):1523–1525. doi: 10.1093/nar/21.7.1523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kim U., Wang Y., Sanford T., Zeng Y., Nishikura K. Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11457–11461. doi: 10.1073/pnas.91.24.11457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Knudson A. G., Jr Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A. 1971 Apr;68(4):820–823. doi: 10.1073/pnas.68.4.820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lau P. P., Chen S. H., Wang J. C., Chan L. A 40 kilodalton rat liver nuclear protein binds specifically to apolipoprotein B mRNA around the RNA editing site. Nucleic Acids Res. 1990 Oct 11;18(19):5817–5821. doi: 10.1093/nar/18.19.5817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Melcher T., Maas S., Higuchi M., Keller W., Seeburg P. H. Editing of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR-B pre-mRNA in vitro reveals site-selective adenosine to inosine conversion. J Biol Chem. 1995 Apr 14;270(15):8566–8570. doi: 10.1074/jbc.270.15.8566. [DOI] [PubMed] [Google Scholar]
  36. Navaratnam N., Bhattacharya S., Fujino T., Patel D., Jarmuz A. L., Scott J. Evolutionary origins of apoB mRNA editing: catalysis by a cytidine deaminase that has acquired a novel RNA-binding motif at its active site. Cell. 1995 Apr 21;81(2):187–195. doi: 10.1016/0092-8674(95)90328-3. [DOI] [PubMed] [Google Scholar]
  37. Navaratnam N., Morrison J. R., Bhattacharya S., Patel D., Funahashi T., Giannoni F., Teng B. B., Davidson N. O., Scott J. The p27 catalytic subunit of the apolipoprotein B mRNA editing enzyme is a cytidine deaminase. J Biol Chem. 1993 Oct 5;268(28):20709–20712. [PubMed] [Google Scholar]
  38. Navaratnam N., Shah R., Patel D., Fay V., Scott J. Apolipoprotein B mRNA editing is associated with UV crosslinking of proteins to the editing site. Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):222–226. doi: 10.1073/pnas.90.1.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Novo F. J., Kruszewski A., MacDermot K. D., Goldspink G., Górecki D. C. Editing of human alpha-galactosidase RNA resulting in a pyrimidine to purine conversion. Nucleic Acids Res. 1995 Jul 25;23(14):2636–2640. doi: 10.1093/nar/23.14.2636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. O'Connell M. A., Krause S., Higuchi M., Hsuan J. J., Totty N. F., Jenny A., Keller W. Cloning of cDNAs encoding mammalian double-stranded RNA-specific adenosine deaminase. Mol Cell Biol. 1995 Mar;15(3):1389–1397. doi: 10.1128/mcb.15.3.1389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Peltz S. W., Brown A. H., Jacobson A. mRNA destabilization triggered by premature translational termination depends on at least three cis-acting sequence elements and one trans-acting factor. Genes Dev. 1993 Sep;7(9):1737–1754. doi: 10.1101/gad.7.9.1737. [DOI] [PubMed] [Google Scholar]
  42. Powell L. M., Wallis S. C., Pease R. J., Edwards Y. H., Knott T. J., Scott J. A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine. Cell. 1987 Sep 11;50(6):831–840. doi: 10.1016/0092-8674(87)90510-1. [DOI] [PubMed] [Google Scholar]
  43. Rueter S. M., Burns C. M., Coode S. A., Mookherjee P., Emeson R. B. Glutamate receptor RNA editing in vitro by enzymatic conversion of adenosine to inosine. Science. 1995 Mar 10;267(5203):1491–1494. doi: 10.1126/science.7878468. [DOI] [PubMed] [Google Scholar]
  44. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Shah R. R., Knott T. J., Legros J. E., Navaratnam N., Greeve J. C., Scott J. Sequence requirements for the editing of apolipoprotein B mRNA. J Biol Chem. 1991 Sep 5;266(25):16301–16304. [PubMed] [Google Scholar]
  46. Sharma P. M., Bowman M., Madden S. L., Rauscher F. J., 3rd, Sukumar S. RNA editing in the Wilms' tumor susceptibility gene, WT1. Genes Dev. 1994 Mar 15;8(6):720–731. doi: 10.1101/gad.8.6.720. [DOI] [PubMed] [Google Scholar]
  47. Skuse G. R., Kosciolek B. A., Rowley P. T. Molecular genetic analysis of tumors in von Recklinghausen neurofibromatosis: loss of heterozygosity for chromosome 17. Genes Chromosomes Cancer. 1989 Sep;1(1):36–41. doi: 10.1002/gcc.2870010107. [DOI] [PubMed] [Google Scholar]
  48. Sommer B., Köhler M., Sprengel R., Seeburg P. H. RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell. 1991 Oct 4;67(1):11–19. doi: 10.1016/0092-8674(91)90568-j. [DOI] [PubMed] [Google Scholar]
  49. Teng B., Burant C. F., Davidson N. O. Molecular cloning of an apolipoprotein B messenger RNA editing protein. Science. 1993 Jun 18;260(5115):1816–1819. doi: 10.1126/science.8511591. [DOI] [PubMed] [Google Scholar]
  50. Xu G. F., O'Connell P., Viskochil D., Cawthon R., Robertson M., Culver M., Dunn D., Stevens J., Gesteland R., White R. The neurofibromatosis type 1 gene encodes a protein related to GAP. Cell. 1990 Aug 10;62(3):599–608. doi: 10.1016/0092-8674(90)90024-9. [DOI] [PubMed] [Google Scholar]
  51. Yamanaka S., Poksay K. S., Balestra M. E., Zeng G. Q., Innerarity T. L. Cloning and mutagenesis of the rabbit ApoB mRNA editing protein. A zinc motif is essential for catalytic activity, and noncatalytic auxiliary factor(s) of the editing complex are widely distributed. J Biol Chem. 1994 Aug 26;269(34):21725–21734. [PubMed] [Google Scholar]
  52. Yang J. H., Sklar P., Axel R., Maniatis T. Editing of glutamate receptor subunit B pre-mRNA in vitro by site-specific deamination of adenosine. Nature. 1995 Mar 2;374(6517):77–81. doi: 10.1038/374077a0. [DOI] [PubMed] [Google Scholar]

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