microRNAs regulate β-catenin of the Wnt signaling pathway in early sea urchin development

Development of complex multicellular organisms requires careful regulation at both transcriptional and post-transcriptional levels. Post-transcriptional gene regulation is in part mediated by a class of non-coding RNAs of 21-25 nucleotides in length known as microRNAs (miRNAs). beta-catenin, regulated by the canonical Wnt signaling pathway, has a highly evolutionarily conserved function in patterning early metazoan embryos, in forming the Anterior-Posterior axis, and in establishing the endomesoderm. Using reporter constructs and site-directed mutagenesis, we identified at least three miRNA binding sites within the 3' untranslated region (3'UTR) of the sea urchin beta-catenin. Further, blocking these three miRNA binding sites within the beta-catenin 3'UTR to prevent regulation of endogenous beta-catenin by miRNAs resulted in a minor increase in beta-catenin protein accumulation that is sufficient to induce aberrant gut morphology and circumesophageal musculature. These phenotypes are likely the result of increased transcript levels of Wnt responsive endomesodermal regulatory genes. This study demonstrates the importance of miRNA regulation of beta-catenin in early development. (C) 2015 Elsevier Inc. All rights reserved.