Open AccessThe MicroRNA mir-71 Inhibits Calcium Signaling by Targeting the TIR-1/Sarm1 Adaptor Protein to Control Stochastic L/R Neuronal Asymmetry in C. elegans
Author(s) -
Ya Ching Hsieh,
Chieh Chang,
Chiou-Fen Chuang
Publication year - 2012
Publication title -
plos genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.587
H-Index - 233
eISSN - 1553-7404
pISSN - 1553-7390
DOI - 10.1371/journal.pgen.1002864
Subject(s) - signal transducing adaptor protein , caenorhabditis elegans , microbiology and biotechnology , biology , signal transduction , rna interference , biochemistry , gene , rna
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.