1. A coding-independent function of an alternative Ube3a transcript during neuronal development
- Author
-
Roberto Fiore, Simon Sumer, Tatjana Wüst, Rainer K.W. Schwarting, Franziska Metge, Dominik Seffer, Markus Wöhr, Ayla Aksoy-Aksel, Silvia Bicker, Jeremy Valluy, Christoph Dieterich, Gerhard Schratt, and Martin Lackinger
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Neurogenesis ,RNA Splicing ,Ubiquitin-Protein Ligases ,Molecular Sequence Data ,Nerve Tissue Proteins ,Biology ,Transfection ,Hippocampus ,Mice ,RNA interference ,microRNA ,Coding region ,Animals ,Humans ,Protein Isoforms ,RNA, Messenger ,RNA, Small Interfering ,Frameshift Mutation ,3' Untranslated Regions ,Genetics ,Neurons ,Gene knockdown ,General Neuroscience ,Miniature Postsynaptic Potentials ,RNA ,Excitatory Postsynaptic Potentials ,Dendrites ,Non-coding RNA ,Cell biology ,Rats ,RNA silencing ,MicroRNAs ,HEK293 Cells ,Protein Biosynthesis ,RNA splicing ,RNA Interference - 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.
- Published
- 2015