PUBLICATION
MicroRNA degradation by a conserved target RNA regulates animal behavior
- Authors
- Bitetti, A., Mallory, A.C., Golini, E., Carrieri, C., Carreño Gutiérrez, H., Perlas, E., Pérez-Rico, Y.A., Tocchini-Valentini, G.P., Enright, A.J., Norton, W.H.J., Mandillo, S., O'Carroll, D., Shkumatava, A.
- ID
- ZDB-PUB-180228-7
- Date
- 2018
- Source
- Nature structural & molecular biology 25(3): 244-251 (Journal)
- Registered Authors
- Bitetti, Angelo, Norton, Will, Shkumatava, Alena
- Keywords
- none
- Datasets
- GEO:GSE98707
- MeSH Terms
-
- Animals
- Anxiety
- Behavior, Animal*
- Binding Sites
- Brain/metabolism
- Cerebellum/metabolism
- Mice
- MicroRNAs/metabolism*
- RNA, Long Noncoding/chemistry
- RNA, Long Noncoding/metabolism
- RNA, Messenger/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 29483647 Full text @ Nat. Struct. Mol. Biol.
Citation
Bitetti, A., Mallory, A.C., Golini, E., Carrieri, C., Carreño Gutiérrez, H., Perlas, E., Pérez-Rico, Y.A., Tocchini-Valentini, G.P., Enright, A.J., Norton, W.H.J., Mandillo, S., O'Carroll, D., Shkumatava, A. (2018) MicroRNA degradation by a conserved target RNA regulates animal behavior. Nature structural & molecular biology. 25(3):244-251.
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, 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping