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 (ąsd; 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 (ąsd; n?=?3; p?<?0.05).
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