Figure 5. Loss of miR-19b results in dysregulation of cardiac ion currents.

(a) qRT-PCR revealed dysregulation of various cardiac ion channels in miR-19b-deficient zebrafish. Transcripts with a predicted miR-19b binding site in its 3′-UTR are indicated in blue (±sd; n = 3 from 15 pooled embryos per sample; p < 0,05). (b) Illustration of a mammalian action potential with corresponding currents and genes. (c,d) Potential miR-19b targets were tested for direct regulation by a dual luciferase reporter gene assay. 3′UTR of indicated zebrafish (c) and human (d) genes was cloned downstream of a luciferase gene. Luciferase expression was normalized to renilla expression. As control, target sites were mutated to reverse miR-19b-induced repression. KCNE4, KCNJ2 and SCN1B proved to be direct targets in zebrafish and in humans. Additionally, the 3′UTR of human SCN4B showed responsiveness to miR-19b (±sd; n = 3; p < 0.05).