Nonsense-mediated mRNA decay among coagulation factor genes

Document Type: Review Article

Author

Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Abstract

Objective(s): Haemostasis prevents blood loss following vascular injury. It depends on the unique concert of events involving platelets and specific blood proteins, known as coagulation factors. The clotting system requires precise regulation and coordinated reactions to maintain the integrity of the vasculature. Clotting insufficiency mostly occurs due to genetically inherited coagulation factor deficiencies such as hemophilia.
Materials and Methods: A relevant literature search of PubMed was performed using the keywords coagulation factors, Nonsense-mediated mRNA decay and premature translation termination codons. Search limitations included English language and human-based studies.
Results: Mutations that cause premature translation termination codons probably account for one-third of genetically inherited diseases. Transcripts bearing aberrant termination codons are selectively identified and eliminated by an evolutionarily conserved posttranscriptional pathway known as nonsense-mediated mRNA decay (NMD). There are many pieces of evidence of decay among coagulation factor genes. However, the hemophilia gene (F8) does not seem to be subjected to NMD. Since the F8 gene is located on the X-chromosome, a connection between X-linked traits and mRNA decay could be assumed.
Conclusion: Considering that not all genes go through decay, this review focuses on the basics of the mechanism in coagulation genes. It is interesting to determine whether this translation-coupled surveillance system represents a general rule for the genes encoding components of the same physiological cascade.

Keywords


1. Mann KG. Biochemistry and physiology of blood coagulation. Thromb Haemost 1999; 82:165-174.

2. Davie EW. Biochemical and molecular aspects of the coagulation cascade. Thromb Haemost 1995; 74:1-6.

3. Davie EW, Fujikawa K, Kisiel W. The coagulation cascade: initiation, maintenance, and regulation. Biochemistry 1991; 30:10363-10370.

4. Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev 2013; 93:327-358.

5. Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arterioscler Thromb Vasc Biol 2007; 27:1687-1693.

6. Mackman N. Role of tissue factor in hemostasis, thrombosis, and vascular development. Arterioscler Thromb Vasc Biol 2004; 24:1015-1022.

7. Maly MA, Tomasov P, Hajek P, Blasko P, Hrachovinova I, Salaj P, et al. The role of tissue factor in thrombosis and hemostasis. Physiol Res 2007; 56:685-696.

8. Eilertsen KE, Osterud B. Tissue factor: (patho)physiology and cellular biology. Blood Coagul Fibrinolysis 2004; 15:521-538.

9. Gailani D, Renne T. Intrinsic pathway of coagulation and arterial thrombosis. Arterioscler Thromb Vasc Biol 2007; 27:2507-2513.

10. Gailani D, Renne T. The intrinsic pathway of coagulation: a target for treating thromboembolic disease? J Thromb Haemost 2007; 5:1106-1112.

11. Muller F, Gailani D, Renne T. Factor XI and XII as antithrombotic targets. Curr Opin Hematol 2011; 18:349-355.

12. Walsh PN. Platelet coagulation-protein interactions. Semin Thromb Hemost 2004; 30:461-471.

13. Lowenberg EC, Meijers JC, Monia BP, Levi M. Coagulation factor XI as a novel target for antithrombotic treatment. J Thromb Haemost 2010; 8:2349-2357.

14. Saenko EL, Shima M, Sarafanov AG. Role of activation of the coagulation factor VIII in interaction with vWf, phospholipid, and functioning within the factor Xase complex. Trends Cardiovasc Med 1999; 9:185-192.

15. Stassen JM, Arnout J, Deckmyn H. The hemostatic system. Curr Med Chem 2004; 11:2245-2260.

16. Peyvandi F, Jayandharan G, Chandy M, Srivastava A, Nakaya SM, Johnson MJ, et al. Genetic diagnosis of haemophilia and other inherited bleeding disorders. Haemophilia 2006; 12:82-89.

17. Peyvandi F, Cattaneo M, Inbal A, De Moerloose P, Spreafico M. Rare bleeding disorders. Haemophilia 2008; 14:202-210.

18. Shahbazi S, Moghaddam-Banaem L, Ekhtesari F, Ala FA. Impact of inherited bleeding disorders on pregnancy and postpartum hemorrhage. Blood Coagul Fibrinolysis 2012; 23:603-607.

19. Bowen DJ. Haemophilia A and haemophilia B: molecular insights. Mol Pathol 2002; 55:127-144.

20. van Schooten CJ, Shahbazi S, Groot E, Oortwijn BD, van den Berg HM, Denis CV, et al. Macrophages contribute to the cellular uptake of von Willebrand factor and factor VIII in vivo. Blood 2008; 112:1704-1712.

21. Bolton-Maggs PH, Pasi KJ. Haemophilias A and B. Lancet 2003; 361:1801-1809.

22. Thompson AR. Molecular biology of the hemophilias. Prog Hemost Thromb 1991; 10:175-214.

23. Berntorp E, Boulyjenkov V, Brettler D, Chandy M, Jones P, Lee C, et al. Modern treatment of haemophilia. Bull World Health Organ 1995; 73:691-701.

24. Thompson AR. Structure, function, and molecular defects of factor IX. Blood 1986; 67:565-572.

25. McGraw RA, Davis LM, Lundblad RL, Stafford DW, Roberts HR. Structure and function of factor IX: defects in haemophilia B. Clin Haematol 1985; 14:359-383.

26. Sommer SS, Scaringe WA, Hill KA. Human germline mutation in the factor IX gene. Mutat Res 2001; 487:1-17.

27. Duga S, Salomon O. Congenital factor XI deficiency: an update. Semin Thromb Hemost 2013; 39:621-631.

28. Seligsohn U. Factor XI deficiency in humans. J Thromb Haemost 2009; 7:84-87.

29. Hsieh L, Nugent D. Factor XIII deficiency. Haemophilia 2008; 14:1190-1200.

30. Biswas A, Ivaskevicius V, Seitz R, Thomas A, Oldenburg J. An update of the mutation profile of Factor 13 A and B genes. Blood Rev 2011; 25:193-204.

31. Perry DJ. Factor VII Deficiency. Br J Haematol 2002; 118:689-700.

32. Mariani G, Bernardi F. Factor VII deficiency. Semin Thromb Hemost 2009; 35:400-406.

33. Menegatti M, Peyvandi F. Factor X deficiency. Semin Thromb Hemost 2009; 35:407-415.

34. Uprichard J, Perry DJ. Factor X deficiency. Blood Rev 2002; 16:97-110.

35. Ardillon L, Lefrancois A, Graveleau J, Fouassier M, Ternisien C, Sigaud M, et al. Management of bleeding in severe factor V deficiency with a factor V inhibitor. Vox Sang 2014; 107:97-99.

36. Lenting PJ, Christophe OD, Denis CV. von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends. Blood 2015; 125:2019-2028.

37. Shahbazi S, Alavi S, Mahdian R. Classification of exon 18 linked variants of VWF gene in von Willebrand disease. Int J Mol Epidemiol Genet 2012; 3:77-83.

38. Bryckaert M, Rosa JP, Denis CV, Lenting PJ. Of von Willebrand factor and platelets. Cell Mol life Sci 2015; 27:307-326.

39. Shahbazi S, Mahdian R, Ala FA, Lavergne JM, Denis CV, Christophe OD. Molecular characterization of Iranian patients with type 3 von Willebrand disease. Haemophilia 2009; 15:1058-1064.

40. Shahbazi S, Lenting PJ, Fribourg C, Terraube V, Denis CV, Christophe OD. Characterization of the interaction between von Willebrand factor and osteoprotegerin. J Thromb Haemost 2007; 5:1956-1962.

41. Mannucci PM. Treatment of von Willebrand's Disease. N Engl J Med 2004; 351:683-694.

42. Shahbazi S, Baniahmad F, Zakiani-Roudsari M, Raigani M, Mahdian R. Nonsense mediated decay of VWF mRNA subsequent to c.7674-7675insC mutation in type3 VWD patients. Blood Cells Mol Dis 2012; 49:48-52.

43. Baumann M, Pontiller J, Ernst W. Structure and basal transcription complex of RNA polymerase II core promoters in the mammalian genome: an overview. Mol Biotechnol 2010; 45:241-247.

44. Miller JN, Pearce DA. Nonsense-mediated decay in genetic disease: friend or foe? Mutat Res Rev Mutat Res 2014; 762:52-64.

45. Zhang J, Sun X, Qian Y, Maquat LE. Intron function in the nonsense-mediated decay of beta-globin mRNA: indications that pre-mRNA splicing in the nucleus can influence mRNA translation in the cytoplasm. RNA 1998; 4:801-815.

46. Koenig M, Beggs AH, Moyer M, Scherpf S, Heindrich K, Bettecken T, et al. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet 1989; 45:498-506.

47. Karam R, Wilkinson M. A conserved microRNA/NMD regulatory circuit controls gene expression. RNA Biol 2012; 9:22-26.

48. Mikkola H, Syrjala M, Rasi V, Vahtera E, Hamalainen E, Peltonen L, et al. Deficiency in the A-subunit of coagulation factor XIII: two novel point mutations demonstrate different effects on transcript levels. Blood 1994; 84:517-525.

49. Montefusco MC, Duga S, Asselta R, Santagostino E, Mancuso G, Malcovati M, et al. A novel two base pair deletion in the factor V gene associated with severe factor V deficiency. Br J Haematol 2000; 111:1240-1246.

50. Solda G, Asselta R, Ghiotto R, Tenchini ML, Castaman G, Duga S. A type II mutation (Glu117stop), induction of allele-specific mRNA degradation and factor XI deficiency. Haematologica 2005; 90:1716-1718.

51. Nichols WC, Lyons SE, Harrison JS, Cody RL, Ginsburg D. Severe von Willebrand disease due to a defect at the level of von Willebrand factor mRNA expression: detection by exonic PCR-restriction fragment length polymorphism analysis. Proc Natl Acad Sci U S A 1991; 88:3857-3861.

52. Mohlke KL, Nichols WC, Rehemtulla A, Kaufman RJ, Fagerstrom HM, Ritvanen KL, et al. A common frameshift mutation in von Willebrand factor does not alter mRNA stability but interferes with normal propeptide processing. Br J Haematol 1996; 95:184-191.

53. Plate M, Duga S, Baronciani L, La Marca S, Rubini V, Mannucci PM, et al. Premature termination codon mutations in the von Willebrand factor gene are associated with allele-specific and position-dependent mRNA decay. Haematologica 2010; 95:172-174.

54. Castaman G, Plate M, Giacomelli SH, Rodeghiero F, Duga S. Alterations of mRNA processing and stability as a pathogenic mechanism in von Willebrand factor quantitative deficiencies. J Thromb Haemost 2010; 8:2736-2742.

55. Corrales I, Ramirez L, Altisent C, Parra R, Vidal F. The study of the effect of splicing mutations in von Willebrand factor using RNA isolated from patients' platelets and leukocytes. J Thromb Haemost 2011; 9:679-688.

56. David D, Santos IM, Johnson K, Tuddenham EG, McVey JH. Analysis of the consequences of premature termination codons within factor VIII coding sequences. J Thromb Haemost 2003; 1:139-146.

57. Zimmermann MA, Oldenburg J, Muller CR, Rost S. Expression studies of mutant factor VIII alleles with premature termination codons with regard to inhibitor formation. Haemophilia 2014; 20:e215-221.

58. Martorell L, Corrales I, Ramirez L, Parra R, Raya A, Barquinero J, et al. Molecular characterization of ten F8 splicing mutations in RNA isolated from patient's leucocytes: assessment of in silico prediction tools accuracy. Haemophilia 2015; 21:249-257.

59. Castaman G, Giacomelli SH, Mancuso ME, Sanna S,
Santagostino E, Rodeghiero F. F8 mRNA studies in haemophilia A patients with different splice site mutations. Haemophilia 2010; 16:786-790.

60. Yin S, Deng W, Zheng H, Zhang Z, Hu L, Kong X. Evidence that the nonsense-mediated mRNA decay pathway participates in X chromosome dosage compensation in mammals. Biochem Biophys Res Commun 2009; 383:378-382.