MicroRNA degradation by a conserved target RNA regulates animal behavior

Nat Struct Mol Biol. 2018 Mar;25(3):244-251. doi: 10.1038/s41594-018-0032-x. Epub 2018 Feb 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

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


  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger