title: The microRNA mir-71 inhibits calcium signaling by targeting the TIR-1/Sarm1 adaptor protein to control stochastic L/R neuronal asymmetry in C. elegans.
abstract: The Caenorhabditis elegans left and right AWC olfactory neurons communicate to establish stochastic asymmetric identities, AWC(ON) and AWC(OFF), by inhibiting a calcium-mediated signaling pathway in the future AWC(ON) cell. NSY-4/claudin-like protein and NSY-5/innexin gap junction protein are the two parallel signals that antagonize the calcium signaling pathway to induce the AWC(ON) fate. However, it is not known how the calcium signaling pathway is downregulated by nsy-4 and nsy-5 in the AWC(ON) cell. Here we identify a microRNA, mir-71, that represses the TIR-1/Sarm1 adaptor protein in the calcium signaling pathway to promote the AWC(ON) identity. Similar to tir-1 loss-of-function mutants, overexpression of mir-71 generates two AWC(ON) neurons. tir-1 expression is downregulated through its 3' UTR in AWC(ON), in which mir-71 is expressed at a higher level than in AWC(OFF). In addition, mir-71 is sufficient to inhibit tir-1 expression in AWC through the mir-71 complementary site in the tir-1 3' UTR. Our genetic studies suggest that mir-71 acts downstream of nsy-4 and nsy-5 to promote the AWC(ON) identity in a cell autonomous manner. Furthermore, the stability of mature mir-71 is dependent on nsy-4 and nsy-5. Together, these results provide insight into the mechanism by which nsy-4 and nsy-5 inhibit calcium signaling to establish stochastic asymmetric AWC differentiation.
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center Research Foundation, Cincinnati, Ohio, United States of America.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Hsieh
authors.forename: Chieh
authors.initials: C
authors.lastname: Chang
authors.forename: Chiou-Fen
authors.initials: CF
authors.lastname: Chuang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D020013:Calcium Signaling / Q000235:genetics*; D002450:Cell Communication; D002454:Cell Differentiation; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D020871:RNA Stability; D043562:Receptors, G-Protein-Coupled
chemical_list: D020413:3' Untranslated Regions; D029742:Caenorhabditis elegans Proteins; D017630:Connexins; D003598:Cytoskeletal Proteins; C575438:MIRN71 microRNA, C elegans; D035683:MicroRNAs; D043562:Receptors, G-Protein-Coupled; C521128:inx-19 protein, C elegans; C485906:tir-1 protein, C elegans; D049452:Green Fluorescent Proteins