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MicroRNA degradation by a conserved target RNA regulates animal behavior

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.

 

Nrep-directed miR-29b degradation restricts the microRNA expression domain in the mouse cerebellum. Genetic disruption of the miR-29 site embedded in the Nrep transcript results in expanded miR-29b expression and impaired coordination and motor learning.This work identifies the first in vivo example of an endogenous transcript regulating a miRNA and shows that disruption of this regulatory event has a phenotypic outcome.
Nrep-directed miR-29b degradation restricts the microRNA expression domain in the mouse cerebellum. Genetic disruption of the miR-29 site embedded in the Nrep transcript results in expanded miR-29b expression and impaired coordination and motor learning.This work identifies the first in vivo example of an endogenous transcript regulating a miRNA and shows that disruption of this regulatory event has a phenotypic outcome.

 

Abstract
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 miR29-binding site is located within the 3 UTR. We show that the near-perfect miRNA site selectively triggers miR29b destabilization through 3 trimming and restricts its spatial expression in the cerebellum. Genetic disruption of the miR29 site within mouse Nrep results in ectopic expression of cerebellar miR29b 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