2. Academic Validation
  3. A coding-independent function of an alternative Ube3a transcript during neuronal development

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.
Jeremy Valluy 1,  Silvia Bicker 1,  Ayla Aksoy-Aksel 1,  Martin Lackinger 1,  Simon Sumer 1,  Roberto Fiore 1,  Tatjana Wüst 2,  Dominik Seffer 3,  Franziska Metge 4,  Christoph Dieterich 4,  Markus Wöhr 3,  Rainer Schwarting 3,  Gerhard Schratt 1
Affiliations

Affiliations

  • 1 Institute of Physiological Chemistry, Biochemical-Pharmacological Center Marburg, Philipps University Marburg, Marburg, Germany.
  • 2 Interdisciplinary Center for Neurosciences, SFB488 Junior Group, University Heidelberg, Heidelberg, Germany.
  • 3 Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-University Marburg, Marburg, Germany.
  • 4 Max Planck Institute for Biology of Ageing, Computational RNA Biology Lab, Cologne, Germany.
PMID: 25867122 DOI: 10.1038/nn.3996
Abstract

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.

Figures