Early LQT2 nonsense mutation generates N-terminally truncated hERG channels with altered gating properties by the reinitiation of translation

Journal of Molecular and Cellular Cardiology

Volumn 53, Issue 5, 2012, Pages 725-733

  Stump, Matthew R ^a   Gong, Qiuming ^a   Packer, Jonathan D ^a   Zhou, Zhengfeng ^a  

^a OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

Author keywords

Cardiac arrhythmias; Ion channels; Long QT syndrome; Patch clamp

Indexed keywords

MESSENGER RNA; POTASSIUM CHANNEL HERG;

ACTION POTENTIAL; AMINO TERMINAL SEQUENCE; ARTICLE; CHANNEL GATING; CONTROLLED STUDY; FRAMESHIFT MUTATION; GENE; GENE CONTROL; GENE EXPRESSION; GENE FUNCTION; GENE INACTIVATION; GENE LOSS; GENE STRUCTURE; GENETIC TRANSCRIPTION; HEART REPOLARIZATION; HERG GENE; HUMAN; HUMAN CELL; LONG QT SYNDROME; LQT2 GENE; MOLECULAR MECHANICS; MUTATIONAL ANALYSIS; NONSENSE MUTATION; PRIORITY JOURNAL; Q18X GENE; RNA ANALYSIS; SITE DIRECTED MUTAGENESIS; TRANSLATION INITIATION;

BASE SEQUENCE; CODON, NONSENSE; ETHER-A-GO-GO POTASSIUM CHANNELS; HEK293 CELLS; HUMANS; KINETICS; LONG QT SYNDROME; MEMBRANE POTENTIALS; NONSENSE MEDIATED MRNA DECAY; PATCH-CLAMP TECHNIQUES; PEPTIDE CHAIN TERMINATION, TRANSLATIONAL; PEPTIDE FRAGMENTS; PROTEIN BIOSYNTHESIS; RNA, MESSENGER;

EID: 84867403969     PISSN: 00222828     EISSN: 10958584     Source Type: Journal    
DOI: 10.1016/j.yjmcc.2012.08.021     Document Type: Article

References (45)

1. Kr potassium channel. Cell 1995, 81:299-307.
2. Trudeau M.C., Warmke J.W., Ganetzky B., Robertson G.A. HERG, a human inward rectifier in the voltage-gated potassium channel family. Science 1995, 269:92-95.
3. Schwartz P.J., Periti M., Malliani A. The long Q-T syndrome. Am Heart J 1975, 89:378-390.
4. Sanguinetti M.C. HERG1 channelopathies. Pflugers Arch 2010, 460:265-276.
5. Splawski I., Shen J., Timothy K.W., Lehmann M.H., Priori S., Robinson J.L., et al. Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation 2000, 102:1178-1185.
6. Tester D.J., Will M.L., Haglund C.M., Ackerman M.J. Compendium of cardiac channel mutations in 541 consecutive unrelated patients referred for long QT syndrome genetic testing. Heart Rhythm 2005, 2:507-517.
7. Napolitano C., Priori S.G., Schwartz P.J., Bloise R., Ronchetti E., Nastoli J., et al. Genetic testing in the long QT syndrome: development and validation of an efficient approach to genotyping in clinical practice. JAMA 2005, 294:2975-2980.
8. Nagaoka I., Shimizu W., Itoh H., Yamamoto S., Sakaguchi T., Oka Y., et al. Mutation site dependent variability of cardiac events in Japanese LQT2 form of congenital long-QT syndrome. Circ J 2008, 72:694-699.
9. Kapplinger J.D., Tester D.J., Salisbury B.A., Carr J.L., Harris-Kerr C., Pollevick G.D., et al. Spectrum and prevalence of mutations from the first 2,500 consecutive unrelated patients referred for the FAMILION long QT syndrome genetic test. Heart Rhythm 2009, 6:1297-1303.
10. Gong Q., Zhang L., Vincent G.M., Horne B.D., Zhou Z. Nonsense mutations in hERG cause a decrease in mutant mRNA transcripts by nonsense-mediated mRNA decay in human long-QT syndrome. Circulation 2007, 116:17-24.
11. Zarraga I.G., Zhang L., Stump M.R., Gong Q., Vincent G.M., Zhou Z. Nonsense-mediated mRNA decay caused by a frameshift mutation in a large kindred of type 2 long QT syndrome. Heart Rhythm 2011, 8:1200-1206.
12. Maquat L.E. Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics. Nat Rev Mol Cell Biol 2004, 5:89-99.
13. Chang Y.F., Imam J.S., Wilkinson M.F. The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem 2007, 76:51-74.
14. Gong Q., Keeney D.R., Robinson J.C., 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.
15. Bhuiyan Z.A., Momenah T.S., Gong Q., Amin A.S., Ghamdi S.A., Carvalho J.S., et al. Recurrent intrauterine fetal loss due to near absence of HERG: clinical and functional characterization of a homozygous nonsense HERG Q1070X mutation. Heart Rhythm 2008, 5:553-561.
16. Gong Q., Stump M.R., Zhou Z. Inhibition of nonsense-mediated mRNA decay by antisense morpholino oligonucleotides restores functional expression of hERG nonsense and frameshift mutations in long-QT syndrome. J Mol Cell Cardiol 2011, 50:223-229.
17. Nagy E., Maquat L.E. A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance. Trends Biochem Sci 1998, 23:198-199.
18. Kozak M. Constraints on reinitiation of translation in mammals. Nucleic Acids Res 2001, 29:5226-5232.
19. Rinne T., Clements S.E., Lamme E., Duijf P.H., Bolat E., Meijer R., et al. A novel translation re-initiation mechanism for the p63 gene revealed by amino-terminal truncating mutations in Rapp-Hodgkin/Hay-Wells-like syndromes. Hum Mol Genet 2008, 17:1968-1977.
20. Neu-Yilik G., Amthor B., Gehring N.H., Bahri S., Paidassi H., Hentze M.W., et al. Mechanism of escape from nonsense-mediated mRNA decay of human beta-globin transcripts with nonsense mutations in the first exon. RNA 2011, 17:843-854.
21. Claycomb W.C., Lanson N.A., Stallworth B.S., Egeland D.B., Delcarpio J.B., Bahinski A., et al. HL-1 cells: a cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte. Proc Natl Acad Sci U S A 1998, 95:2979-2984.
22. Abramoff M., Magelhaes P., Ram S. Image processing with ImageJ. Biophotonics Int. 2004, 11:36-44.
23. Zhou Z., Gong Q., Epstein M.L., January C.T. HERG channel dysfunction in human long QT syndrome. Intracellular transport and functional defects. J Biol Chem 1998, 273:21061-21066.
24. Stump M.R., Gong Q., Zhou Z. Multiple splicing defects caused by hERG splice site mutation 2592+1G>A associated with long QT syndrome. Am J Physiol Heart Circ Physiol 2011, 300:H312-H318.
25. Sale H., Wang J., O'Hara T.J., Tester D.J., Phartiyal P., He J.Q., et al. Physiological properties of hERG 1a/1b heteromeric currents and a hERG 1b-specific mutation associated with long-QT syndrome. Circ Res 2008, 103:e81-e95.
26. Smith P.L., Baukrowitz T., Yellen G. The inward rectification mechanism of the HERG cardiac potassium channel. Nature 1996, 379:833-836.
27. Larsen A.P., Olesen S.P., Grunnet M., Jespersen T. Characterization of hERG1a and hERG1b potassium channels-a possible role for hERG1b in the I (Kr) current. Pflugers Arch 2008, 456:1137-1148.
28. Gianulis E.C., Trudeau M.C. Rescue of aberrant gating by a genetically encoded PAS (Per-Arnt-Sim) domain in several long QT syndrome mutant human ether-a-go-go-related gene potassium channels. J Biol Chem 2011, 286:22160-22169.
29. Inoue K., Khajavi M., Ohyama T., Hirabayashi S., Wilson J., Reggin J.D., et al. Molecular mechanism for distinct neurological phenotypes conveyed by allelic truncating mutations. Nat Genet 2004, 36:361-369.
30. Wang J., Trudeau M.C., Zappia A.M., Robertson G.A. Regulation of deactivation by an amino terminal domain in human ether-a-go-go-related gene potassium channels. J Gen Physiol 1998, 112:637-647.
31. Schonherr R., Heinemann S.H. Molecular determinants for activation and inactivation of HERG, a human inward rectifier potassium channel. J Physiol 1996, 493(Pt 3):635-642.
32. Chen J., Zou A., Splawski I., Keating M.T., Sanguinetti M.C. Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG potassium channels accelerate channel deactivation. J Biol Chem 1999, 274:10113-10118.
33. Ishigaki Y., Li X., Serin G., Maquat L.E. Evidence for a pioneer round of mRNA translation: mRNAs subject to nonsense-mediated decay in mammalian cells are bound by CBP80 and CBP20. Cell 2001, 106:607-617.
34. Zhang J., Maquat L.E. Evidence that translation reinitiation abrogates nonsense-mediated mRNA decay in mammalian cells. EMBO J 1997, 16:826-833.
35. Buisson M., Anczukow O., Zetoune A.B., Ware M.D., Mazoyer S. The 185delAG mutation (c.68_69delAG) in the BRCA1 gene triggers translation reinitiation at a downstream AUG codon. Hum Mutat 2006, 27:1024-1029.
36. Puel A., Reichenbach J., Bustamante J., Ku C.L., Feinberg J., Doffinger R., et al. The NEMO mutation creating the most-upstream premature stop codon is hypomorphic because of a reinitiation of translation. Am J Hum Genet 2006, 78:691-701.
37. Paulsen M., Lund C., Akram Z., Winther J.R., Horn N., Moller L.B. Evidence that translation reinitiation leads to a partially functional Menkes protein containing two copper-binding sites. Am J Hum Genet 2006, 79:214-229.
38. Pedersen A.G., Nielsen H. Neural network prediction of translation initiation sites in eukaryotes: perspectives for EST and genome analysis. Proc Int Conf Intell Syst Mol Biol 1997, 5:226-233.
39. Morais Cabral J.H., Lee A., Cohen S.L., Chait B.T., Li M., Mackinnon R. Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain. Cell 1998, 95:649-655.
40. + channel deactivation gating from the solution structure of the EAG domain. J Biol Chem 2011, 286:6184-6191.
41. Ng C.A., Hunter M.J., Perry M.D., Mobli M., Ke Y., Kuchel P.W., et al. The N-terminal tail of hERG contains an amphipathic alpha-helix that regulates channel deactivation. PLoS One 2011, 6:e16191.
42. Kr channel. J Gen Physiol 1996, 107:611-619.
43. Sanguinetti M.C., Xu Q.P. Mutations of the S4-S5 linker alter activation properties of HERG potassium channels expressed in Xenopus oocytes. J Physiol 1999, 514(Pt 3):667-675.
44. Wang J., Myers C.D., Robertson G.A. Dynamic control of deactivation gating by a soluble amino-terminal domain in HERG K(+) channels. J Gen Physiol 2000, 115:749-758.
45. Gustina A.S., Trudeau M.C. A recombinant N-terminal domain fully restores deactivation gating in N-truncated and long QT syndrome mutant hERG potassium channels. Proc Natl Acad Sci U S A 2009, 106:13082-13087.