title: microRNAs regulate β-catenin of the Wnt signaling pathway in early sea urchin development.
abstract: 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). β-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 β-catenin. Further, blocking these three miRNA binding sites within the β-catenin 3'UTR to prevent regulation of endogenous β-catenin by miRNAs resulted in a minor increase in β-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 β-catenin in early development.
authors.affiliation: Department of Biological Sciences, University of Delaware, 323 Wolf Hall, Newark, DE 19716, USA.
authors.forename: Nadezda
authors.initials: N
authors.lastname: Stepicheva
authors.affiliation: Department of Biological Sciences, University of Delaware, 323 Wolf Hall, Newark, DE 19716, USA.
authors.forename: Priya A
authors.initials: PA
authors.lastname: Nigam
authors.affiliation: Department of Biological Sciences, University of Delaware, 323 Wolf Hall, Newark, DE 19716, USA.
authors.forename: Archana D
authors.initials: AD
authors.lastname: Siddam
authors.affiliation: Department of Biology, University of Miami, Coral Gables, FL 33124, USA.
authors.forename: Chieh Fu
authors.initials: CF
authors.lastname: Peng
authors.affiliation: Department of Biological Sciences, University of Delaware, 323 Wolf Hall, Newark, DE 19716, USA. Electronic address: jsong@udel.edu.
authors.forename: Jia L
authors.initials: JL
authors.lastname: Song
mesh_terms: D020413:3' Untranslated Regions; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D019521:Body Patterning / Q000235:genetics; D004707:Endoderm / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007422:Intestines / Q000196:embryology; D008648:Mesoderm / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D009841:Oligonucleotides / Q000737:chemistry; D010641:Phenotype; D012617:Sea Urchins / Q000196:embryology*; D047270:Strongylocentrotus purpuratus; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D009841:Oligonucleotides; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D000469:Alkaline Phosphatase
keywords: Circumesophageal muscles; Endoderm; Larval gut; Mesoderm; PMCs; Post-transcriptional regulation; Sea urchin; Target protectors