Alternative polyadenylation signals in the 3′ non-coding region of a voltage-gated potassium channel gene are major determinants of mRNA isoform expression

We investigated the role of the 3′ non-coding region of a mouse voltage-gated potassium channel mRNA (mKv1.4 mRNA) in post-transcriptional regulation of gene expression. In contrast to an earlier report from studies carried out in Xenopus oocytes, we found that 3′ non-coding region sequences of mKv1.4 mRNAs did not significantly affect expression of a heterologous reporter RNA in vitro or in mammalian cells/cell lines. Instead, our data revealed a possible role for alternative polyadenylation mediated by distinct determinants ∼ 0.2 kb and ∼ 1.2 kb downstream of the Kv1.4 coding region. The use of the downstream polyadenylation signal correlated with the synthesis of a larger Kv1.4 mRNA isoform that was more abundantly expressed than the smaller mRNA species, whose expression was regulated by the upstream polyadenylation signal. Our results suggest that the relative strengths of the polyadenylation signals are major determinants of overall Kv1.4 mRNA abundance in cells.