Details

Autor(en) / Beteiligte

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

Titel

MicroRNA degradation by a conserved target RNA regulates animal behavior

Ist Teil von

• Nature structural & molecular biology, 2018-03, Vol.25 (3), p.244

Ort / Verlag

United States

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.