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Regulation Of Kv11.1 Potassium Channel C-Terminal Isoform Expression By The Rna-Binding Proteins Hur And Hud, Qiuming Gong, Matthew R. Stump, Zhengfeng Zhou
Regulation Of Kv11.1 Potassium Channel C-Terminal Isoform Expression By The Rna-Binding Proteins Hur And Hud, Qiuming Gong, Matthew R. Stump, Zhengfeng Zhou
Faculty Publications - Department of Biological & Molecular Science
The potassium voltage-gated channel subfamily H member 2 (KCNH2) gene encodes the Kv11.1 potassium channel, which conducts the rapidly activating delayed rectifier current in the heart. KCNH2 pre-mRNA undergoes alternative polyadenylation and forms a functional, full-length Kv11.1a isoform if exon 15 is polyadenylated or a nonfunctional, C-terminally truncated Kv11.1a-USO isoform if intron 9 is polyadenylated. The molecular mechanisms that regulate Kv11.1 isoform expression are poorly understood. In this study, using HEK293 cells and reporter gene expression, pulldown assays, and RNase protection assays, we identified the RNA-binding proteins Hu antigen R (HuR) and Hu antigen D (HuD) as regulators of Kv11.1 …
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 …