The lincRNAs in Vertebrate Development (Inserm/CNRS/Institut Curie) team headed by Alena Shkumatava is interested in the roles that Long intervening noncoding RNAs play in cellular complexity and development. Researchers published in Nature Structural & Molecular Biology revue.
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, weshow 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.
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 and Alena Shkumatava