shrikant anant et al.

Further studies demonstrated that CUGBP2 is a competitive inhibitor of the RNA-editing reaction, which can be rescued by addition of either increasing amounts of apobec-1 or ACF, but not apoB RNA (68). This suggests that CUGBP2 exerts its effects by disrupting the apobec-1-ACF interaction. Further, protein-protein interaction and enzyme kinetic studies are required to fully deduce the mechanism of CUGBP2 action in the RNA-editing process.

a. CUGBP2: mRNA Splicing, Stability, and Translational Control Functions? In addressing its potential biological functions, it is worth emphasizing that CUGBP2 is ubiquitously expressed at low levels, but at higher levels in skeletal and cardiac muscle, sites where neither apobec-1 or apoB RNA is expressed and no C to U RNA editing occurs (68). An important feature in myotonic dystrophy is muscle wasting and weakness, features that emerge in the setting of expanded CUG repeats within the myotonic dystrophy-related protein kinase, DMPK (122). These expanded CUG repeats were initially postulated to bind to proteins and sequester them in the nucleus, resulting in loss of their normal RNA processing function. Indeed, CUGBP2 was initially identified to bind to the expanded CUG triplet repeats present in the 3'UTR of DMPK (121).

What cellular function of CUGBP2 is disrupted in myotonic dystrophy? CUGBP2 was identified to bind and regulate alternative splicing of the human cardiac troponin T pre-mRNA (123-125). The observation that splicing of cardiac troponin T is also disrupted in striated muscle of myotonic dystrophy patients, implies indirectly that CUGBP2 may exert a role in alternative splicing in this setting (126-128). In this regard, it should be noted that a muscle-specific chloride channel, CIC-1, and insulin receptor pre-mRNAs are aberrantly spliced in striated muscle of myotonic dystrophy patients (126,129,130). The mechanistic relationship of these observations to disease pathogenesis will require further study. Adding to the complexity in this disease, there is increased expression of CUGBP1, a homolog of CUGBP2, in the muscle of myotonic dystrophy patients (126). CUGBP1 is also implicated in the aberrant splicing function (126,131), and its role in the setting of myotonic dystrophy will need further direct evaluation. More recently, CUGBP2 has been demonstrated to modulate mRNA stability and translation functions (132). CUGBP2 was observed to bind AU-rich sequences in the 3'UTR of cyclooxygenase-2 mRNA and stabilize the mRNA, yet paradoxically inhibits its translation (132). Furthermore, CUGBP2 overexpression in a colon cancer cell line, HT-29, resulted in apoptosis, suggesting an important role for this protein in cell turnover and proliferation (132). Taken together, these studies suggest that CUGBP2 and its homologs may play a role in various cellular functions, including regulating apoB mRNA editing in epithelial cells as well as possibly in disorders associated with altered RNA splicing and translation.

C. Additional Factors—Regulators of RNA Editing?

Four cellular proteins have been identified either as a apobec-1 RNA-binding protein (ABBP-1, ABBP-2, hnRNP-C) or a member of the editosome complex (AUX240).

ABBP-1 is an alternatively spliced variant of hnRNP-A/B, which was originally identified in a two-hybrid screen of a human placenta cDNA library (71). Confirmation of apobec-1 interaction was performed by immunopreci-pitation assays using in vitro translated proteins (71). In addition, the apobec-1-binding domain in ABBP-1 was mapped to a glycine-rich region, located in the C-terminus of the protein (71). ABBP-1 was also observed to bind apoB RNA in vitro by electrophoretic mobility shift assays (71). Immunodepletion of ABBP-1 in extracts from apobec-1-transfected HepG2 cells reduced apoB RNA editing in vitro (71). Furthermore, antisense cDNA-mediated knockdown of ABBP-1 in HepG2 cells resulted in loss of endogenous apoB mRNA editing (71). Taken together these data suggest that ABBP-1 or another spliced variant of hnRNP-A/B is required for apoB mRNA editing. These findings are intriguing in light of the information that HepG2 cells express ACF, the required complementation factor for C to U editing. The immediate question is how ABBP1 knockdown abrogates apoB RNA editing since ACF itself should continue to be expressed and has been demonstrated alone to complement apobec-1. Further analysis of these ABBP-1 antisense experiments may reveal whether the inhibition was specific for ABBP-1 downregulation or whether ACF expression was inadvertently altered.

ABBP-2 (also known as HEDJ) also identified in a yeast two-hybrid screen of a human placenta library (70). This protein was originally identified as a member of the hsp40 cochaperone family, which is characterized by the presence of a highly conserved J domain involved in protein synthesis, folding, and secretion (70,133). The J domain is a signature of members of the DNAJ family. These chaperones are also involved in reverse translocation and degradation of misfolded proteins in the lumen of the endoplasmic reticulum (133). The J domain interacts with the endoplasmic reticulum-associated Hsp70 in an ATP-dependent manner and is capable of stimulating its ATPase activity (70,133). It is intriguing that apobec-1 interacts with this protein. Similar to ABBP-1, inhibition of ABBP-2/HEDJ expression by transfection of an antisense ABBP-2 cDNA resulted in downregulation of apoB RNA editing

(70). The mechanism of this response is unclear and additional studies will need to address the effects of ABBP-2 expression on the expression and function of ACF.


hnRNP-C1 was identified in a yeast two-hybrid screen of a rat liver cDNA library using apobec-1 as bait (67). hnRNP-C1 is an AU-rich RNA-binding protein that binds to nascent transcripts and is involved in spliceosomal assembly and mRNA splicing (134,135). Recombinant hnRNP-C1 bound to the sense strand of apoB RNA, but not the antisense strand (67). Given that apoB RNA is ~ 70% AU-rich in content in the region flanking the edited cytidine, this RNA-binding activity profile suggests that hnRNP-C1 interacts with a specific AU-rich sequence in apoB RNA (67). Further studies narrowed the RNA-binding domain to the N-terminal 104 amino acids in hnRNP-C1, which contains a single RRM (67). Recombinant hnRNP-C1 was observed to inhibit C to U RNA editing, catalyzed by a partially purified fraction from rat liver extracts (67). The mechanism of this competitive inhibition was not due to binding of hnRNP-C1 to apoB RNA, since a deletion mutant of hnRNP-C1 that retained RNA-binding activity, but lacked the leucine-rich repeats, failed to inhibit the RNA-editing reaction (67). Rather, the findings suggest that hnRNP-C1 competitively inhibits apoB RNA editing through protein-protein interactions with apobec-1 and/or other factors in the holoenzyme.

4. AUX240

AUX240 was identified in rat liver extracts using monoclonal antibodies generated against the 27S editosome that was assembled in vitro on a synthetic apoB RNA (72). Immunodepletion of AUX240 from rat liver extracts resulted in significant inhibition of C to U RNA-editing activity (72). Furthermore, addition of the bead-eluted material to rat liver extracts enhanced RNA-editing efficiency (72). However, addition of the immunoadsorbed material alone to the editing reaction in the absence of the additional proteins did not demonstrate any RNA-editing activity (72). These data suggest that the immunoadsorbed material does not contain all the factors necessary to support C to U RNA editing. Taken together, these data offer no clear proof of the involvement of AUX240 in C to U RNA-editing activity. It should be noted that multiple proteins from rat liver extracts coeluted with AUX240 from rat liver extracts, including a protein of 66 kDa which may conceivably be ACF (72). The nature of these other coeluting proteins is currently unknown, but further study will likely be revealing.

V. Summary

C to U editing of a single cytidine at nt 6666 in apoB RNA is mediated by a multicomponent-editing complex, and is regulated by developmental, nutritional, and hormonal factors. Apobec-1 and ACF are components of the minimal-editing enzyme, although other proteins, such as GRY-RBP and CUGBP2, represent likely auxiliary factors of the editing holoenzyme that regulate its activity. Much work remains in this area, including identification of all the factors that comprise the holoenzyme and a characterization of their role in C to U RNA editing. In addition, as implied throughout this report, the proteins that have been currently identified may exhibit other functions in RNA metabolism. It would be interesting to determine whether these other functions, such as pre-mRNA splicing, mRNA stability, and mRNA translation, are related to their intrinsic RNA-editing function. Future studies will likely provide an opportunity to consider these issues in the context of the evolutionary significance of RNA editing and the RNA world.


Work cited from the authors' laboratories is supported by the National Institutes of Health grants DK-56260 and HL-38180 to NOD, DK-62265 to S.A., and the Digestive Disease Research Core Center Grant DK-52574. S.A. is a Research Scholar of the American Gastroenterology Association. The authors acknowledge valuable discussions with current and former laboratory members, particularly Jeff Henderson, Susan Kennedy, Debnath Mukhophadyay, and Libby Newberry.


1. J. M. Gott and R. B. Emeson, Functions and mechanisms of RNA editing, Annu. Rev. Genet. 34, 499-531 (2000).

2. A. P. Gerber and W. Keller, RNA editing by base deamination: more enzymes, more targets, new mysteries, Trends Biochem. Sci. 26, 376-384 (2001).

3. L. Simpson, O. H. Thiemann, N. J. Savill, J. D. Alfonzo and D. A. Maslov, Evolution of RNA editing in trypanosome mitochondria, Proc. Natl. Acad. Sci. USA 97, 6986-6993 (2000).

4. Y. W. Cheng and J. M. Gott, Transcription and RNA editing in a soluble in vitro system from Physarum mitochondria, Nucleic Acids Res. 28, 3695-3701 (2000).

5. Y. W. Cheng, L. M. Visomirski-Robic and J. M. Gott, Non-templated addition of nucleotides to the 3' end of nascent RNA during RNA editing in Physarum, EMBO J. 20, 1405-1414 (2001).

6. M. L. Reed, N. M. Peeters and M. R. Hanson, A single alteration 20 nt 5' to an editing target inhibits chloroplast RNA editing in vivo, Nucleic Acids Res. 29, 1507-1513 (2001).

7. R. Bock, Sense from nonsense: how the genetic information of chloroplasts is altered by RNA editing, Biochimie 82, 549-557 (2000).

8. T. Hirose and M. Sugiura, Involvement of a site-specific trans-acting factor and a common RNA-binding protein in the editing of chloroplast mRNAs: development of a chloroplast in vitro RNA editing system, EMBO J. 20, 1144-1152 (2001).

9. P. Giege and A. Brennicke, RNA editing in Arabidopsis mitochondria effects 441 C to U changes in ORFs, Proc. Natl. Acad. Sci. USA 96, 15324-15329 (1999).

10. P. H. Seeburg, A-to-I editing: new and old sites, functions and speculations, Neuron 35,17-20 (2002).

11. J. Villegas, I. Muller, J. Arredondo, R. Pinto and L. O. Burzio, A putative RNA editing from U to C in a mouse mitochondrial transcript, Nucleic Acids Res. 30, 1895-1901 (2002).

12. P. M. Sharma, M. Bowman, S. L. Madden, F. J. Rauscher, 3rd and S. Sukumar, RNA editing in the Wilms' tumor susceptibility gene, WT1, Genes Dev. 8, 720-731 (1994).

13. K. B. Gunning, S. L. Cohn, G. E. Tomlinson, L. C. Strong and V. Huff, Analysis of possible WT1 RNA processing in primary Wilms tumors, Oncogene 13, 1179-1185 (1996).

14. C. Mrowka and A. Schedl, Wilms' tumor suppressor gene WT1: from structure to renal pathophysiologic features, J. Am. Soc. Nephrol 11 Suppl. 16, S106-S115 (2000).

15. J. Villegas, A. M. Zarraga, I. Muller, L. Montecinos, E. Werner, M. Brito, A. M. Meneses and L. O. Burzio, A novel chimeric mitochondrial RNA localized in the nucleus of mouse sperm, DNA Cell Biol 19, 579-588 (2000).

16. S. G. Young, Recent progress in understanding apolipoprotein B, Circulation 82, 1574-1594

17. N. O. Davidson and G. S. Shelness, Apolipoprotein B: mRNA editing, lipoprotein assembly, and presecretory degradation, Annu. Rev. Nutr. 20, 169-193 (2000).

18. C. Hadjiagapiou, F. Giannoni, T. Funahashi, S. F. Skarosi and N. O. Davidson, Molecular cloning of a human small intestinal apolipoprotein B mRNA editing protein, Nucleic Acids Res. 22, 1874-1879 (1994).

19. P. P. Lau, H. J. Zhu, A. Baldini, C. Charnsangavej and L. Chan, Dimeric structure of a human apolipoprotein B mRNA editing protein and cloning and chromosomal localization of its gene, Proc. Natl Acad. Sci. USA 91, 8522-8526 (1994).

20. J. Greeve, I. Altkemper, J. H. Dieterich, H. Greten and E. Windler, Apolipoprotein B mRNA editing in 12 different mammalian species: hepatic expression is reflected in low concentrations of apoB-containing plasma lipoproteins, J. Lipid Res. 34, 1367-1383 (1993).

21. S. Anant and N. O. Davidson, Molecular mechanisms of apolipoprotein B mRNA editing, Curr. Opin. Lipidol. 12, 159-165 (2001).

22. S. Anant, H. Yu and N. O. Davidson, Evolutionary origins of the mammalian apolipoproteinB RNA editing enzyme, apobec-1: structural homology inferred from analysis of a cloned chicken small intestinal cytidine deaminase, Biol. Chem. 379, 1075-1081 (1998).

23. B. Teng and N. O. Davidson, Evolution of intestinal apolipoprotein B mRNA editing. Chicken apolipoprotein B mRNA is not edited, but chicken enterocytes contain in vitro editing enhancement factor(s), J. Biol. Chem. 267, 21265-21272 (1992).

24. L. Powell-Braxton, M. Veniant, R. D. Latvala, K. I. Hirano, W. B. Won, J. Ross, N. Dybdal, C. H. Zlot, S. G. Young, N. O. Davidson, A mouse model of human familial hyper-cholesterolemia: markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow diet, Nat. Med. 4, 934-938 (1998).

25. M. S. Davies, S. C. Wallis, D. M. Driscoll, J. K. Wynne, G. W. Williams, L. M. Powell and J. Scott, Sequence requirements for apolipoprotein B RNA editing in transfected rat hepatoma cells, J. Biol. Chem. 264, 13395-13398 (1989).

26. R. R. Shah, T. J. Knott, J. E. Legros, N. Navaratnam, J. C. Greeve and J. Scott, Sequence requirements for the editing of apolipoprotein B mRNA, J. Biol. Chem. 266, 16301-16304

27. D. M. Driscoll, S. Lakhe-Reddy, L. M. Oleksa and D. Martinez, Induction of RNA editing at heterologous sites by sequences in apolipoprotein B mRNA, Mol Cell. Biol. 13, 7288-7294 (1993).

28. J. W. Backus and H. C. Smith, Three distinct RNA sequence elements are required for efficient apolipoprotein B (apoB) RNA editing in vitro, Nucleic Acids Res. 20, 6007-6014 (1992).

29. M. Hersberger and T. L. Innerarity, Two efficiency elements flanking the editing site of cytidine 6666 in the apolipoprotein B mRNA support mooring-dependent editing, J. Biol. Chem. 273, 9435-9442 (1998).

30. G. R. Skuse, A. J. Cappione, M. Sowden, L. J. Metheny and H. C. Smith, The neurofibromatosis type I messenger RNA undergoes base-modification RNA editing, Nucleic Acids Res. 24, 478-485 (1996).

31. D. Mukhopadhyay, S. Anant, R. M. Lee, S. Kennedy, D. Viskochil and N. O. Davidson, C ! U editing of neurofibromatosis 1 mRNA occurs in tumors that express both the type II transcript and apobec-1, the catalytic subunit of the apolipoprotein B mRNA-editing enzyme, Am. J. Hum. Genet. 70, 38-50 (2002).

32. A. J. Cappione, B. L. French and G. R. Skuse, A potential role for NF1 mRNA editing in the pathogenesis of NF1 tumors, Am. J. Hum. Genet. 60, 305-312 (1997).

33. K. Cichowski and T. Jacks, NF1 tumor suppressor gene function: narrowing the GAP, Cell 104, 593-604 (2001).

34. G. Bollag, D. W. Clapp, S. Shih, F. Adler, Y. Y. Zhang, P. Thompson, B. J. Lange, M. H. Freedman, F. McCormick, T. Jacks, K. Shannon, Loss of NF1 results in activation of the Ras signaling pathway and leads to aberrant growth in haematopoietic cells, Nat. Genet. 12, 144-148 (1996).

35. J. Ross, mRNA stability in mammalian cells, Microbiol Rev. 59, 423-450 (1995).

36. S. Anant and N. O. Davidson, An AU-rich sequence element (UUUN[A/U]U) downstream of the edited C in apolipoprotein B mRNA is a high-affinity binding site for Apobec-1: binding of Apobec-1 to this motif in the 3' untranslated region of c-myc increases mRNA stability, Mol Cell Biol. 20, 1982-1992 (2000).

37. F. Giannoni, S. C. Chou, S. F. Skarosi, M. S. Verp, F. J. Field, R. A. Coleman and N. O. Davidson, Developmental regulation of the catalytic subunit of the apolipoprotein B mRNA editing enzyme (APOBEC-1) in human small intestine, J. Lipid Res. 36, 1664-1675 (1995).

38. S. Yamanaka, M. E. Balestra, L. D. Ferrell, J. Fan, K. S. Arnold, S. Taylor, J. M. Taylor and T. L. Innerarity, Apolipoprotein B mRNA-editing protein induces hepatocellular carcinoma and dysplasia in transgenic animals, Proc. Natl Acad. Sci. USA 92, 8483-8487 (1995).

39. S. Yamanaka, K. S. Poksay, D. M. Driscoll and T. L. Innerarity, Hyperediting of multiple cytidines of apolipoprotein B mRNA by APOBEC-1 requires auxiliary protein(s) but not a mooring sequence motif, J. Biol. Chem. 271, 11506-11510 (1996).

40. N. Navaratnam, D. Patel, R. R. Shah, J. C. Greeve, L. M. Powell, T. J. Knott and J. Scott, An additional editing site is present in apolipoprotein B mRNA, Nucleic Acids Pies. 19,1741-1744 (1991).

41. S. Yamanaka, K. S. Poksay, K. S. Arnold and T. L. Innerarity, A novel translational repressor mRNA is edited extensively in livers containing tumors caused by the transgene expression of the apoB mRNA-editing enzyme, Genes Dev. 11, 321-333 (1997).

42. S. Yamanaka, X. Y. Zhang, M. Maeda, K. Miura, S. Wang, R. V. Farese, Jr., H. Iwao and T. L. Innerarity, Essential role of NAT1/p97/DAP5 in embryonic differentiation and the retinoic acid pathway, EMBO J. 19, 5533-5541 (2000).

43. X. Qian, M. E. Balestra, S. Yamanaka, J. Boren, I. Lee and T. L. Innerarity, Low expression of the apolipoprotein B mRNA-editing transgene in mice reduces LDL levels but does not cause liver dysplasia or tumors, Arterioscler. Thromb. Vasc. Biol. 18, 1013-1020 (1998).

44. K. Hirano, S. G. Young, R. V. Farese, Jr., J. Ng, E. Sande, C. Warburton, L. M. Powell-Braxton and N. O. Davidson, Targeted disruption of the mouse apobec-1 gene abolishes apolipoprotein B mRNA editing and eliminates apolipoprotein B48, J. Biol. Chem. 271, 9887-9890 (1996).

45. J. R. Morrison, C. Paszty, M. E. Stevens, S. D. Hughes, T. Forte, J. Scott and E. M. Rubin, Apolipoprotein B RNA editing enzyme-deficient mice are viable despite alterations in lipoprotein metabolism, Proc. Natl. Acad. Sci. USA 93, 7154-7159 (1996).

46. M. Hersberger, S. Patarroyo-White, X. Qian, K. S. Arnold, L. Rohrer, M. E. Balestra and T. L. Innerarity, Regulatable liver expression of the rabbit ApoB mRNA-editing enzyme catalytic polypeptide 1 (APOBEC-1) in mice lacking endogenous APOBEC-1 leads to aberrant hyperediting. Biochem. J. 369, 255-262 (2002).

47. P. P. Lau, D. J. Cahill, H. J. Zhu and L. Chan, Ethanol modulates apolipoprotein B mRNA editing in the rat, J. Lipid Res. 36, 2069-2078 (1995).

48. A. Giangreco, M. P. Sowden, I. Mikityansky and H. C. Smith, Ethanol stimulates apolipoprotein B mRNA editing in the absence of de novo RNA or protein synthesis, Biochem. Biophys. Res. Commun. 289, 1162-1167 (2001).

49. M. P. Sowden, N. Ballatori, K. L. Jensen, L. H. Reed and H. C. Smith, The editosome for cytidine to uridine mRNA editing has a native complexity of 27S: identification of intracellular domains containing active and inactive editing factors, J. Cell Sci. 115, 10271039 (2002).

50. D. Van Mater, M. P. Sowden, J. Cianci, J. D. Sparks, C. E. Sparks, N. Ballatori and H. C. Smith, Ethanol increases apolipoprotein B mRNA editing in rat primary hepatocytes and McArdle cells, Biochem. Biophys. Res. Commun. 252, 334-339 (1998).

51. Y. Yang, M. P. Sowden and H. C. Smith, Induction of cytidine to uridine editing on cytoplasmic apolipoprotein B mRNA by overexpressing APOBEC-1, J. Biol. Chem. 275, 22663-22669 (2000).

52. T. Funahashi, F. Giannoni, A. M. DePaoli, S. F. Skarosi and N. O. Davidson, Tissue-specific, developmental and nutritional regulation of the gene encoding the catalytic subunit of the rat apolipoprotein B mRNA editing enzyme: functional role in the modulation of apoB mRNA editing, J. Lipid Res. 36, 414-428 (1995).

53. Y. Inui, F. Giannoni, T. Funahashi and N. O. Davidson, REPR and complementation factor(s) interact to modulate rat apolipoprotein B mRNA editing in response to alterations in cellular cholesterol flux, J. Lipid Res. 35, 1477-1489 (1994).

54. B. Teng, M. Verp, J. Salomon and N. O. Davidson, Apolipoprotein B messenger RNA editing is developmentally regulated and widely expressed in human tissues, J. Biol. Chem. 265, 20616-20620 (1990).

55. C. L. Baum, B. B. Teng and N. O. Davidson, Apolipoprotein B messenger RNA editing in the rat liver. Modulation by fasting and refeeding a high carbohydrate diet, J. Biol. Chem. 265, 19263-19270 (1990).

56. K. Higuchi, K. Kitagawa, K. Kogishi and T. Takeda, Developmental and age-related changes in apolipoprotein B mRNA editing in mice, J. Lipid Res. 33, 1753-1764 (1992).

57. M. Hersberger, S. Patarroyo-White, K. S. Arnold and T. L. Innerarity, Phylogenetic analysis of the apolipoprotein B mRNA-editing region. Evidence for a secondary structure between the mooring sequence and the 3' efficiency element, J. Biol. Chem. 274, 34590-34597 (1999).

58. K. Bostrom, S. J. Lauer, K. S. Poksay, Z. Garcia, J. M. Taylor and T. L. Innerarity, Apolipoprotein B48 RNA editing in chimeric apolipoprotein EB mRNA, J. Biol. Chem. 264, 15701-15708 (1989).

59. N. Richardson, N. Navaratnam and J. Scott, Secondary structure for the apolipoprotein B mRNA editing site. Au-binding proteins interact with a stem loop, J. Biol. Chem. 273, 31707-31717 (1998).

60. C. Y. Chen and A. B. Shyu, AU-rich elements: characterization and importance in mRNA degradation, Trends Biochem. Sci. 20, 465-470 (1995).

61. P. P. Lau, W. J. Xiong, H. J. Zhu, S. H. Chen and L. Chan, Apolipoprotein B mRNA editing is an intranuclear event that occurs posttranscriptionally coincident with splicing and polyadenylation, J. Biol. Chem. 266, 20550-20554 (1991).

62. M. P. Sowden and H. C. Smith, Commitment of apolipoprotein B RNA to the splicing pathway regulates cytidine-to-uridine editing-site utilization, Biochem. J. 359, 697-705 (2001).

63. H. C. Smith, S. R. Kuo, J. W. Backus, S. G. Harris, C. E. Sparks and J. D. Sparks, In vitro apolipoprotein B mRNA editing: identification of a 27S editing complex, Proc. Natl Acad. Sci. USA 88, 1489-1493 (1991).

64. H. Lellek, R. Kirsten, I. Diehl, F. Apostel, F. Buck and J. Greeve, Purification and molecular cloning of a novel essential component of the apolipoprotein B mRNA editing enzyme-complex, J. Biol. Chem. 275, 19848-19856 (2000).

65. A. Mehta, M. T. Kinter, N. E. Sherman and D. M. Driscoll, Molecular cloning of apobec-1 complementation factor, a novel RNA-binding protein involved in the editing of apolipoprotein B mRNA, Mol. Cell Biol. 20, 1846-1854 (2000).

66. B. Teng, C. F. Burant and N. O. Davidson, Molecular cloning of an apolipoprotein B messenger RNA editing protein, Science 260, 1816-1819 (1993).

67. J. Greeve, H. Lellek, P. Rautenberg and H. Greten, Inhibition of the apolipoprotein B mRNA editing enzyme-complex by hnRNP C1 protein and 40S hnRNP complexes, Biol. Chem. 379, 1063-1073 (1998).

68. S. Anant, J. O. Henderson, D. Mukhopadhyay, N. Navaratnam, S. Kennedy, J. Min and N. O. Davidson, Novel role for RNA-binding protein CUGBP2 in mammalian RNA editing. CUGBP2 modulates C to U editing of apolipoprotein B mRNA by interacting with apobec-1 and ACF, the apobec-1 complementation factor, J. Biol. Chem. 276, 47338-47351 (2001).

69. V. Blanc, N. Navaratnam, J. O. Henderson, S. Anant, S. Kennedy, A. Jarmuz, J. Scott and N. O. Davidson, Identification of GRY-RBP as an apolipoprotein B RNA-binding protein that interacts with both apobec-1 and apobec-1 complementation factor to modulate C to U editing, J. Biol. Chem. 276, 10272-10283 (2001).

70. P. P. Lau, S. H. Chen, J. C. Wang and L. Chan, A 40 kilodalton rat liver nuclear protein binds specifically to apolipoprotein B mRNA around the RNA editing site, Nucleic Acids Res. 18, 5817-5821 (1990).

71. P. P. Lau, H. J. Zhu, M. Nakamuta and L. Chan, Cloning of an Apobec-1-binding protein that also interacts with apolipoprotein B mRNA and evidence for its involvement in RNA editing, J. Biol. Chem. 272, 1452-1455 (1997).

72. D. Schock, S. R. Kuo, M. F. Steinburg, M. Bolognino, J. D. Sparks, C. E. Sparks and H. C. Smith, An auxiliary factor containing a 240-kDa protein complex is involved in apolipoprotein B RNA editing, Proc. Natl. Acad. Sci. USA 93, 1097-1102 (1996).

73. S. Yamanaka, K. S. Poksay, M. E. Balestra, G. Q. Zeng and T. L. Innerarity, 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. 269, 21725-21734 (1994).

74. M. Nakamuta, K. Oka, J. Krushkal, K. Kobayashi, M. Yamamoto, W. H. Li and L. Chan, Alternative mRNA splicing and differential promoter utilization determine tissue-specific expression of the apolipoprotein B mRNA-editing protein (Apobec1) gene in mice. Structure and evolution of Apobec1 and related nucleoside/nucleotide deaminases, J. Biol. Chem. 270, 13042-13056 (1995).

75. P. Hodges and J. Scott, Apolipoprotein B mRNA editing: a new tier for the control of gene expression, Trends Biochem. Sci. 17, 77-81 (1992).

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