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MicroRNA degradation by a conserved target RNA regulates animal behavior

Research output: Contribution to journalArticle

  • Angelo Bitetti
  • Allison C Mallory
  • Elisabetta Golini
  • Claudia Carrieri
  • Héctor Carreño Gutiérrez
  • Emerald Perlas
  • Yuvia A Pérez-Rico
  • Glauco P Tocchini-Valentini
  • Anton J Enright
  • William H J Norton
  • Silvia Mandillo
  • Dónal O'Carroll
  • Alena Shkumatava

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Original languageEnglish
Pages (from-to)244-251
Number of pages8
JournalNature Structural & Molecular Biology
Issue number3
Early online date26 Feb 2018
Publication statusE-pub ahead of print - 26 Feb 2018


Animal microRNAs (miRNAs) repress target transcripts through partial complementarity. By contrast, highly complementary miRNA-binding sites within viral and artificially engineered transcripts induce miRNA degradation in vitro and in cell lines. Here, we show that a genome-encoded transcript harboring a near-perfect and deeply conserved miRNA-binding site for miR-29 controls zebrafish and mouse behavior. This transcript originated in basal vertebrates as a long noncoding RNA (lncRNA) and evolved to the protein-coding gene NREP in mammals, where the miR-29-binding site is located within the 3' UTR. We show that the near-perfect miRNA site selectively triggers miR-29b destabilization through 3' trimming and restricts its spatial expression in the cerebellum. Genetic disruption of the miR-29 site within mouse Nrep results in ectopic expression of cerebellar miR-29b and impaired coordination and motor learning. Thus, we demonstrate an endogenous target-RNA-directed miRNA degradation event and its requirement for animal behavior.

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