Nonsense mutations in hERG cause a decrease in mutant mRNA transcripts by nonsense-mediated mRNA decay in human long-QT syndrome

Circulation

Volumn 116, Issue 1, 2007, Pages 17-24

  Gong, Qiuming ^a   Zhang, Li ^b   Vincent, G Michael ^b   Horne, Benjamin D ^c   Zhou, Zhengfeng ^a,d  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^b LDS HOSPITAL   (United States)

^c UNIVERSITY OF UTAH   (United States)

^d OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

Arrhythmia; Ion channels; Long QT syndrome; Myocytes

Indexed keywords

CYCLOHEXIMIDE; MESSENGER RNA; POTASSIUM CHANNEL HERG;

ADULT; AGED; ANIMAL CELL; ARTICLE; CELL STRAIN HEK293; CLINICAL ARTICLE; CONTROLLED STUDY; FEMALE; GENE EXPRESSION; GENETIC TRANSCRIPTION; HUMAN; HUMAN CELL; LONG QT SYNDROME; LYMPHOCYTE; MALE; NEWBORN; NONHUMAN; NONSENSE MUTATION; PRIORITY JOURNAL; RAT; WILD TYPE;

ADENOVIRIDAE; ADULT; AGED; ANIMALS; ANIMALS, NEWBORN; CELLS, CULTURED; CODON, NONSENSE; CYCLOHEXIMIDE; ETHER-A-GO-GO POTASSIUM CHANNELS; FEMALE; FRAMESHIFT MUTATION; GENES, SYNTHETIC; HUMANS; KIDNEY; LONG QT SYNDROME; LYMPHOCYTES; MALE; MIDDLE AGED; MYOCYTES, CARDIAC; PEDIGREE; POINT MUTATION; PROTEIN SYNTHESIS INHIBITORS; RATS; RATS, SPRAGUE-DAWLEY; RNA INTERFERENCE; RNA, MESSENGER; TRANS-ACTIVATORS; TRANSFECTION;

EID: 34347332362     PISSN: 00097322     EISSN: None     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.107.708818     Document Type: Article

References (35)

1. Schwartz PJ, Periti M, Malliani A. Fundamentals of clinical cardiology: the long QT syndrome. Am Heart J. 1975;89:378-390.
2. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995;80:795-803.
3. Sanguinetti MC, Jiang C, Curran ME, Keating MT. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell. 1995;81:299-307.
4. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT. Spectrum of mutations in long-QT syndrome genes: KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000;102:1178-1185.
5. Napolitano C, Priori SG, Schwartz PJ, Bloise R, Ronchetti E, Nastoli J, Bottelli G, Cerrone M, Leonardi S. Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA. 2005;294:2975-2980.
6. Tester DJ, Will ML, Haglund CM, Ackerman MJ. Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm. 2005;2:507-517.
7. Millat G, Chevalier P, Restier-Miron L, Da Costa A, Bouvagnet P, Kugener B, Fayol L, Gonzalez Armengod C, Oddou B, Chanavat V, Froidefond E, Perraudin R, Rousson R, Rodriguez-Lafrasse C. Spectrum of pathogenic mutations and associated polymorphisms in a cohort of 44 unrelated patients with long QT syndrome. Clin Genet. 2006;70:214-227.
8. +-channel dysfunction in an inherited cardiac arrhythmia. Proc Natl Acad Sci U S A. 1996;93:2208-2212.
9. Zhou Z, Gong Q, Epstein ML, January CT. HERG channel dysfunction in human long QT syndrome: Intracellular transport and functional defects. J Biol Chem. 1998;273:21061-21066.
10. Thomas D, Kiehn J, Katus HA, Karle CA. Defective protein trafficking in hERG-associated hereditary long QT syndrome (LQT2): molecular mechanisms and restoration of intracellular protein processing. Cardiovasc Res. 2003;60:235-232.
11. Delisle BP, Anson BD, Rajamani S, January CT. Biology of cardiac arrhythmias: ion channel protein trafficking. Circ Res. 2004;94:1418-1428.
12. Li X, Xu J, Li M. The human delta1261 mutation of the HERG potassium channel results in a truncated protein that contains a subunit interaction domain and decreases the channel expression. J Biol Chem. 1997;272:705-708.
13. Paulussen A, Yang P, Pangalos M, Verhasselt P, Marrannes R, Verfaille C, Vandenberk I, Crabbe R, Konings F, Luyten W, Armstrong M. Analysis of the human KCNH2 (HERG) gene: identification and characterization of a novel mutation Y667X associated with long QT syndrome and a non-pathological 9 bp insertion. Hum Mutat. 2000;15:483.
14. Kupershmidt S, Yang T, Chanthaphaychith S, Wang Z, Towbin JA, Roden DM. Defective human ether-a-go-go-related gene trafficking linked to an endoplasmic reticulum retention signal in the C terminus. J Biol Chem. 2002;277:27442-27448.
15. Gong Q, Keeney DR, Robinson JC, Zhou Z. Defective assembly and trafficking of mutant HERG channels with C-terminal truncations in long QT syndrome. J Mol Cell Cardiol. 2004;37:1225-1233.
16. Teng S, Ma L, Dong Y, Lin C, Ye J, Bahring R, Vardanyan V, Yang Y, Lin Z, Pongs O, Hui R. Clinical and electrophysiological characterization of a novel mutation R863X in HERG C-terminus associated with long QT syndrome. J Mol Med. 2004;82:189-196.
17. Paulussen AD, Raes A, Jongbloed RJ, Gilissen RA, Wilde AA, Snyders DJ, Smeets HJ, Aerssens J. HERG mutation predicts short QT based on channel kinetics but causes long QT by heterotetrameric trafficking deficiency. Cardiovasc Res. 2005;67:467-475.
18. Kr channel regulation through 14-3-3ε. Hum Mol Genet. 2006;15:2888-2902.
19. Frischmeyer PA, Dietz HC. Nonsense-mediated mRNA decay in health and disease. Hum Mol Genet. 1999;8:1893-1900.
20. Holbrook JA, Neu-Yilik G, Hentze MW, Kulozik AE. Nonsense-mediated decay approaches the clinic. Nat Genet. 2004;36:801-808.
21. Nagy E, Maquat LE. A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance. Trends Biochem Sci. 1998;23:198-199.
22. Maquat LE. Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics. Nat Rev Mol Cell Biol. 2004;5:89-99.
23. Lykke-Andersen J, Shu MD, Steitz JA. Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell. 2000;103:1121-1131.
24. Mendell JT, ap Rhys CM, Dietz HC. Related separable roles for rent1/hUpf1 in altered splicing and decay of nonsense transcripts. Science. 2002;298:419-422.
25. Paillusson A, Hirschi N, Vallan C, Azzalin CM, Muhlemann O. A GFP-based reporter system to monitor nonsense-mediated mRNA decay. Nucleic Acids Res. 2005;33:e54.
26. Zhang L, Timothy KW, Vincent GM, Lehmann MH, Fox J, Giuli LC, Shen J, Splawski I, Priori S, Compton SJ, Yanowitz F, Benhorin J, Moss AJ, Schwartz PJ, Robinson J, Wang Q, Zareba W, Keating M, Towbin JA, Napolitano C, Medina A. Spectrum of ST-T wave patterns and repolarization parameters in congenital long QT syndrome: ECG findings identify genotype. Circulation. 2000;102:2849-2855.
27. Uejima H, Lee MP, Cui H, Feinberg AP. Hot-stop PCR: a simple and general assay for linear quantitation of allele ratios. Nat Genet. 2000;25:375-376.
28. Kurreeman FA, Schonkeren JJ, Heijmans BT, Toes RE, Huizinga TW. Transcription of the IL10 gene reveals allele-specific regulation at the mRNA level. Hum Mol Genet. 2004;13:1755-1762.
29. Gong Q, Keeney DR, Molinari M, Zhou Z. Degradation of trafficking-defective long QT syndrome type II mutant channels by the ubiquitin-proteasome pathway. J Biol Chem. 2005;280:19419-19425.
30. Kapiloff MS, Schillace RV, Westphal AM, Scott JD. mAKAP: an A-kinase anchoring protein targeted to the nuclear membrane of differentiated myocytes. J Cell Sci. 1999;112:2725-2736.
31. Allen-Brady K, Wong J, Camp NJ. PedGenie: an analysis approach for genetic association testing in extended pedigrees and genealogies of arbitrary size. BMC Bioinformatics. 2006;7:209-220.
32. Inoue K, Khajavi M, Ohyama T, Hirabayashi S, Wilson J, Reggin JD, Mancias P, Butler IJ, Wilkinson MF, Wegner M, Lupski JR. Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations. Nat Genet. 2004;36:361-369.
33. Conti E, Izaurralde E. Nonsense-mediated mRNA decay: molecular insights and mechanistic variations across species. Curr Opin Cell Biol. 2005;17:316-325.
34. Dietz HC, McIntosh I, Sakai LY, Corson GM, Chalberg SC, Pyeritz RE, Francomano CA. Four novel FBN1 mutations: significance for mutant transcript level and EGF-like domain calcium binding in the pathogenesis of Marfan syndrome. Genomics. 1993;17:468-475.
35. Moss AJ, Zareba W, Kaufman ES, Gartman E, Peterson DR, Benhorin J, Towbin JA, Keating MT, Priori SG, Schwartz PJ, Vincent GM, Robinson JL, Andrews ML, Feng C, Hall WJ, Medina A, Zhang L, Wang Z. Increased risk of arrhythmic events in long-QT syndrome with mutations in the pore region of the human ether-a-go-go-related gene potassium channel. Circulation. 2002;105:794-799.