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Regulation Of Kv11.1 Isoform Expression By Polyadenylate Binding Protein Nuclear 1, Matthew R. Stump, Rachel T. Nguyen, Rachel H. Drgastin, Delaney Search, Quiming Gong, Zhengfeng Zhou
Regulation Of Kv11.1 Isoform Expression By Polyadenylate Binding Protein Nuclear 1, Matthew R. Stump, Rachel T. Nguyen, Rachel H. Drgastin, Delaney Search, Quiming Gong, Zhengfeng Zhou
Faculty Publications - Department of Biological & Molecular Science
The Kv11.1 voltage-gated potassium channel, encoded by the KCNH2 gene, conducts the rapidly activating delayed rectifier current in the heart. KCNH2 pre-mRNA undergoes alternative polyadenylation to generate two C-terminal Kv11.1 isoforms in the heart. Utilization of a poly(A) signal in exon 15 produces the full-length, functional Kv11.1a isoform, while intron 9 polyadenylation generates the C-terminally truncated, nonfunctional Kv11.1a-USO isoform. The relative expression of Kv11.1a and Kv11.1a-USO isoforms plays an important role in the regulation of Kv11.1 channel function. In this study, we tested the hypothesis that the RNA polyadenylate binding protein nuclear 1 (PABPN1) interacts with a unique 22 nt …
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 …
Upregulation Of Functional Kv11.1 Isoform Expression By Inhibition Of Intronic Polyadenylation With Antisense Morpholino Oligonucleotides, Qiuming Gong, Matthew R. Stump, Zhengfeng Zhou
Upregulation Of Functional Kv11.1 Isoform Expression By Inhibition Of Intronic Polyadenylation With Antisense Morpholino Oligonucleotides, Qiuming Gong, Matthew R. Stump, Zhengfeng Zhou
Faculty Publications - Department of Biological & Molecular Science
The KCNH2 gene encodes the Kv11.1 potassium channel that conducts the rapidly activating delayed rectifier current in the heart. KCNH2 pre-mRNA undergoes alternative processing; intron 9 splicing leads to the formation of a functional, full-length Kv11.1a isoform, while polyadenylationwithin intron 9 generates a non-functional, Cterminally truncated Kv11.1a-USO isoform. The relative expression of Kv11.1 isoforms plays an important role in the regulation of Kv11.1 channel function and the pathogenesis of long QT syndrome. In this study,we identified cis-acting elements that are required for KCNH2 intron 9 poly(A) signal activity. Mutation of these elements decreased Kv11.1a-USO expression and increased the expression of …