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Alternative splicing determines mRNA translation initiation and function of human K 2P 10.1 K + channels
Author(s) -
Staudacher Kathrin,
Baldea Ioana,
Kisselbach Jana,
Staudacher Ingo,
Rahm AnnKathrin,
Schweizer Patrick A.,
Becker Rüdiger,
Katus Hugo A.,
Thomas Dierk
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2011.210666
Subject(s) - messenger rna , ion channel , rna splicing , translation (biology) , alternative splicing , microbiology and biotechnology , biology , membrane potential , potassium channel , biophysics , chemistry , biochemistry , rna , gene , receptor
Non‐technical summary The resting membrane potential of excitable cells such as neurones and cardiac myocytes depends on the distribution of potassium ions across the cell membrane. Specialized membrane proteins called K 2P 10.1 ion channels pass potassium ions and stabilize membranes of excitable cells at hyperpolarizing potentials below the threshold for action potential firing. Alternative mRNA translation initiation (ATI) contributes to K 2P 10.1 protein diversity: Ribosomal synthesis of K 2P 10.1 channel proteins harbouring different N‐terminal domains initiated from two downstream mRNA start codons regulates K 2P 10.1 function. We now demonstrate that splicing determines translation start sites of human K 2P 10.1 mRNA via recombination of short nucleotide signalling sequences preceding the first start mRNA codon, revealing a novel biological mechanism. Our study suggests that tissue‐specific K 2P 10.1 ion channel mRNA splicing and translation initiation determines the resting membrane potential and contributes to electrophysiological plasticity of neuronal and cardiac cells.