MicroRNA degradation by a conserved target RNA regulates animal behavior

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

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

microRNAs (miRNAs) repress target transcripts through partial complementarity. By contrast, highly complementary miRNAbinding 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.
Original languageEnglish
Pages (from-to)244-251
Number of pages8
JournalNature Structural & Molecular Biology
Early online date26 Feb 2018
Publication statusPublished - 1 Mar 2018


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