A coding-independent function of an alternative Ube3a transcript during neuronal development

Nat Neurosci. 2015 May;18(5):666-73. doi: 10.1038/nn.3996. Epub 2015 Apr 13.


The E3 ubiquitin ligase Ube3a is an important regulator of activity-dependent synapse development and plasticity. Ube3a mutations cause Angelman syndrome and have been associated with autism spectrum disorders (ASD). However, the biological significance of alternative Ube3a transcripts generated in mammalian neurons remains unknown. We report here that Ube3a1 RNA, a transcript that encodes a truncated Ube3a protein lacking catalytic activity, prevents exuberant dendrite growth and promotes spine maturation in rat hippocampal neurons. Surprisingly, Ube3a1 RNA function was independent of its coding sequence but instead required a unique 3' untranslated region and an intact microRNA pathway. Ube3a1 RNA knockdown increased activity of the plasticity-regulating miR-134, suggesting that Ube3a1 RNA acts as a dendritic competing endogenous RNA. Accordingly, the dendrite-growth-promoting effect of Ube3a1 RNA knockdown in vivo is abolished in mice lacking miR-134. Taken together, our results define a noncoding function of an alternative Ube3a transcript in dendritic protein synthesis, with potential implications for Angelman syndrome and ASD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Dendrites / ultrastructure
  • Excitatory Postsynaptic Potentials / physiology
  • Frameshift Mutation
  • HEK293 Cells
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Humans
  • Mice
  • MicroRNAs / genetics
  • Miniature Postsynaptic Potentials / physiology
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Neurogenesis / genetics*
  • Neurons / ultrastructure
  • Protein Biosynthesis
  • Protein Isoforms / genetics
  • Protein Isoforms / physiology
  • RNA Interference
  • RNA Splicing
  • RNA, Messenger / genetics
  • RNA, Messenger / physiology*
  • RNA, Small Interfering / pharmacology
  • Rats
  • Transfection
  • Ubiquitin-Protein Ligases / genetics*


  • 3' Untranslated Regions
  • MicroRNAs
  • Nerve Tissue Proteins
  • Protein Isoforms
  • RNA, Messenger
  • RNA, Small Interfering
  • Ube3a protein, rat
  • Ubiquitin-Protein Ligases

Associated data

  • GENBANK/KP742805