Nonsense-Mediated mRNA Decay of hERG Mutations in Long QT Syndrome

Methods Mol Biol. 2018:1684:37-49. doi: 10.1007/978-1-4939-7362-0_4.

Abstract

Long QT syndrome type 2 (LQT2) is caused by mutations in the human ether-à-go-go related gene (hERG), which encodes the Kv11.1 potassium channel in the heart. Over 30% of identified LQT2 mutations are nonsense or frameshift mutations that introduce premature termination codons (PTCs). Contrary to intuition, the predominant consequence of LQT2 nonsense and frameshift mutations is not the production of truncated proteins, but rather the degradation of mutant mRNA by nonsense-mediated mRNA decay (NMD), an RNA surveillance mechanism that selectively eliminates the mRNA transcripts that contain PTCs. In this chapter, we describe methods to study NMD of hERG nonsense and frameshift mutations in long QT syndrome.

Keywords: KCNH2; Long QT syndrome; Nonsense-mediated mRNA decay; Potassium channel.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Codon, Nonsense*
  • ERG1 Potassium Channel / genetics*
  • Frameshift Mutation*
  • Genetic Predisposition to Disease
  • HEK293 Cells
  • Humans
  • Long QT Syndrome / genetics*
  • Nonsense Mediated mRNA Decay*
  • Patch-Clamp Techniques

Substances

  • Codon, Nonsense
  • ERG1 Potassium Channel
  • KCNH2 protein, human

Supplementary concepts

  • Long Qt Syndrome 2