microRNA-138 modulates cardiac patterning during embryonic development

Abstract

Organ patterning during embryonic development requires precise temporal and spatial regulation of protein activity. microRNAs (miRNAs), small noncoding RNAs that typically inhibit protein expression, are broadly important for proper development, but their individual functions during organogenesis are largely unknown. We report that miR-138 is expressed in specific domains in the zebrafish heart and is required to establish appropriate chamber-specific gene expression patterns. Disruption of miR-138 function led to ventricular expansion of gene expression normally restricted to the atrio-ventricular valve region and, ultimately, to disrupted ventricular cardiomyocyte morphology and cardiac function. Temporal-specific knockdown of miR-138 by antagomiRs showed miR-138 function was required during a discrete developmental window, 24 -34 h post-fertilization (hpf). miR-138 functioned partially by repressing the retinoic acid synthesis enzyme, aldehyde dehydrogenase-1a2, in the ventricle. This activity was complemented by miR-138-mediated ventricular repression of the gene encoding versican (cspg2), which was positively regulated by retinoic-acid signaling. Our findings demonstrate that miR-138 helps establish discrete domains of gene expression during cardiac morphogenesis by targeting multiple members of a common pathway, and also establish the use of antagomiRs in fish for temporal knockdown of miRNA function.heart development ͉ organ patterning ͉ retinoic acid ͉ atrioventricular canal ͉ versican

miR-449a Regulates the Chondrogenesis of Human Mesenchymal Stem Cells Through Direct Targeting of Lymphoid Enhancer-Binding Factor-1

“…Small molecules of 17-23 nucleotides in length, microRNAs have been found to be involved in various processes, including cell proliferation [9,10], apoptosis [11,12], immunoresponses [13], protein expression [14][15][16], and tissue development [17][18][19][20][21][22][23]. By forming a functional RNA-induced silencing complex [24], microRNAs recognize a complementary sequence of the target genes' 3¢ untranslated region (UTR) region and induce the inhibition of gene expression by 1 of 2 mechanisms: mRNA cleavage [25] or translational repression [26].…”

Interactions between microRNAs and long non-coding RNAs in cardiac development and repair

“…Locked nucleic acid (LNA)-antagomiRsmediated knockdown of miR-195 in neonatal mice resulted in higher number of proliferating cardiomyocytes, while the overexpression of miR-195 led to right ventricular hypoplasia as well as ventricular septal defects [44]. Similarly, other miRs were shown to have an important role in the final phases of cardiac maturation, both for cardiomyocyte maturation (miR-138-1 and miR-138 [45]) and ventricular wall development (miR-130a and miR-130b [46]). …”

Knockdown of versican 1 blocks cigarette-induced loss of insoluble elastin in human lung fibroblasts

“…Moreover, versican is also regulated by several microRNAs (Morton et al, 2008;Wang et al, 2010;Rutnam et al, 2013). Versican expression, however, has been reported to be inhibited by cadmium chloride, a component of CSE (Chambers et al, 2013).…”