Ion channel messenger RNA processing defects and arrhythmia

Figures & data

Table 1 Abnormal mRNA processing associated with arrhythmia

Gene	Causes	Effect	Disease	Reference
SCN5A	Abnormal expression of splicing factors	Abnormal AS with increased variants VC and VD	HF-associated arrhythmia	9,11
SCN5A	Intron 27 splice site insertion	Activation of cryptic 5′ ss in exon 27	BrS	47
SCN5A	Intron 27 splice site insertion	Activation of cryptic 5′ ss in exon 25, cryptic 3′ ss in exon 26 and intron 25 retention	BrS	48,49
SCN5A	Unknown	Abnormal AS with neonatal exon 6 expression	BrS	50
HCN4	Intron 2 splice site insertion	Abnormal AS with open reading frame shift	BrS	59,60
KCNQI	Exon 7 splice site mutation	Abnormal AS with exon skipping	LQTS	62,63
KCNQI	Intron 7 splice site mutation	Abnormal AS with exon skipping	LQT1	64
KCNQI	Intron 9 splice site mutation	Abnormal AS with exon skipping	LQTS	65
hERG	Intron 9 branch point mutation	Abnormal AS with activation of cryptic splice site in intron 9	LQT2	68
hERG	Intron 10 splice site mutation	Multiple splicing defects	LQTS	69,70
hERG	Intron 9 splice site mutation	Abnormal AS with activation of cryptic 5′ ss in intron 9	LQTS	71
CACNAIC	Exon 14 splice site mutation	Abnormal AS with exon skipping	BrS	72
KCNJ2	Decreased expression of miR-1	increased Kir2.1 mRNA stability	AF	79
CTGF	Decreased expression of miR-133, miR-30	increased CTGF mRNA stability and fibrosis	AF	80

Abbreviations: AF, atrial fibrillation; AS, alternative splicing; ss, splice site; CTGF, connective tissue growth factor; HF, heart failure; BrS, Brugada syndrome; LQTS, long QT syndrome; mRNA, messenger RNA.

Figure 1 A diagram of the mRNA processing pathway. The initial primary RNA transcript (pre-mRNA) synthesized by RNA polymerase II needs to be extensively processed into mature mRNAs before it can be exported out of the nucleus and into the cytoplasm for translation. Processing steps include 5′ capping, pre-mRNA splicing, 3′-end cleavage, and polyadenylation. Once RNA nuclear processing is complete, the capped, spliced, and polyadenylated mRNA is exported from the nucleus to the cytoplasm through nuclear pore complexes. The mature mRNA is translated into protein or is degraded in the cytoplasm. Altered steps known to cause arrhythmia are labeled.

Abbreviations: mRNA, messenger RNA; Pol II, polymerase II.