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Upregulation Of Functional Kv11.1a Isoform Expression By Modified U1 Small Nuclear Rna, Qiuming Gong, Matthew R. Stump, Zhengfeng Zhou
Upregulation Of Functional Kv11.1a Isoform Expression By Modified U1 Small Nuclear Rna, Qiuming Gong, Matthew R. Stump, Zhengfeng Zhou
Faculty Publications - Department of Biological & Molecular Science
The KCNH2 or human ether-a go-go-related gene (hERG) encodes the Kv11.1 potassium channel that conducts the rapidly activating delayed rectifier potassium current in the heart. The expression of Kv11.1 C-terminal isoforms is directed by the alternative splicing and polyadenylation of intron 9. Splicing of intron 9 leads to the formation of a functional, full-length Kv11.1a isoform and polyadenylation of intron 9 results in the production of a non-functional, C-terminally truncated Kv11.1a-USO isoform. The relative expression of Kv11.1a and Kv11.1a-USO plays an important role in regulating Kv11.1 channel function. In the heart, only one-third of KCNH2 pre-mRNA is processed to Kv11.1a …
Position Of Premature Termination Codons Determines Susceptibility Of Herg Mutations To Nonsense-Mediated Mrna Decay In Long Qt Syndrome, Qiuming Gong, Matthew R. Stump, Zhengfeng Zhou
Position Of Premature Termination Codons Determines Susceptibility Of Herg Mutations To Nonsense-Mediated Mrna Decay In Long Qt Syndrome, Qiuming Gong, Matthew R. Stump, Zhengfeng Zhou
Faculty Publications - Department of Biological & Molecular Science
The degradation of human ether-a-go-go-related gene (hERG, KCNH2) transcripts containing premature termination codon (PTC)mutations by nonsense-mediatedmRNA decay (NMD) is an importantmechanismof long QT syndrome type 2 (LQT2). The mechanisms governing the recognition of PTC-containing hERG transcripts asNMD substrates have not been established. We used a minigene system to study two frameshift mutations, R1032Gfs*25 and D1037Rfs*82. R1032Gfs*25 introduces a PTC in exon 14, whereas D1037Rfs*82 causes a PTC in the last exon (exon 15). We showed that R1032Gfs*25, but not D1037Rfs*82, reduced the level of mutant mRNA compared to thewild-type minigene in an NMD-dependent manner. The deletion of intron 14 prevented …