The mir-84 and let-7 paralogous microRNA genes of Caenorhabditis elegans direct the cessation of molting via the conserved nuclear hormone receptors NHR-23 and NHR-25
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作者:
Hayes, Gabriel D.
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机构:Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA
Hayes, Gabriel D.
Frand, Alison R.
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机构:Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA
Frand, Alison R.
Ruvkun, Gary
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Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USAHarvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA
Ruvkun, Gary
[1
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机构:
[1] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA
[2] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
The let-7 microRNA ( miRNA) gene of Caenorhabditis elegans controls the timing of developmental events. let-7 is conserved throughout bilaterian phylogeny and has multiple paralogs. Here, we show that the paralog mir-84 acts synergistically with let-7 to promote terminal differentiation of the hypodermis and the cessation of molting in C. elegans. Loss of mir-84 exacerbates phenotypes caused by mutations in let-7, whereas increased expression of mir-84 suppresses a let-7 null allele. Adults with reduced levels of mir-84 and let-7 express genes characteristic of larval molting as they initiate a supernumerary molt. mir-84 and let-7 promote exit from the molting cycle by regulating targets in the heterochronic pathway and also nhr-23 and nhr-25, genes encoding conserved nuclear hormone receptors essential for larval molting. The synergistic action of miRNA paralogs in development may be a general feature of the diversified miRNA gene family.