ZFIN ID: ZDB-PUB-180228-7
MicroRNA degradation by a conserved target RNA regulates animal behavior
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.
Date: 2018
Source: Nature structural & molecular biology   25(3): 244-251 (Journal)
Registered Authors: Bitetti, Angelo, Norton, Will, Shkumatava, Alena
Keywords: none
Microarrays: 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.
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.