A novel pathway regulates social hierarchy via lncRNA AtLAS and postsynaptic synapsin IIb

Cell Res. 2020 Feb;30(2):105-118. doi: 10.1038/s41422-020-0273-1. Epub 2020 Jan 20.

Abstract

Dominance hierarchy is a fundamental phenomenon in grouped animals and human beings, however, the underlying regulatory mechanisms remain elusive. Here, we report that an antisense long non-coding RNA (lncRNA) of synapsin II, named as AtLAS, plays a crucial role in the regulation of social hierarchy. AtLAS is decreased in the prefrontal cortical excitatory pyramidal neurons of dominant mice; consistently, silencing or overexpression of AtLAS increases or decreases the social rank, respectively. Mechanistically, we show that AtLAS regulates alternative polyadenylation of synapsin II gene and increases synapsin 2b (syn2b) expression. Syn2b reduces AMPA receptor (AMPAR)-mediated excitatory synaptic transmission through a direct binding with AMPAR at the postsynaptic site via its unique C-terminal sequence. Moreover, a peptide disrupting the binding of syn2b with AMPARs enhances the synaptic strength and social ranks. These findings reveal a novel role for lncRNA AtLAS and its target syn2b in the regulation of social behaviors by controlling postsynaptic AMPAR trafficking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Hierarchy, Social
  • Mice, Knockout
  • Models, Biological
  • Polyadenylation
  • Prefrontal Cortex / metabolism
  • Protein Binding
  • Protein Isoforms / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Receptors, AMPA / metabolism
  • Signal Transduction*
  • Synapses / metabolism*
  • Synapsins / metabolism*

Substances

  • Protein Isoforms
  • RNA, Long Noncoding
  • Receptors, AMPA
  • Synapsins