RAI1 Regulates Activity-Dependent Nascent Transcription and Synaptic Scaling

Cell Rep. 2020 Aug 11;32(6):108002. doi: 10.1016/j.celrep.2020.108002.


Long-lasting forms of synaptic plasticity such as synaptic scaling are critically dependent on transcription. Activity-dependent transcriptional dynamics in neurons, however, remain incompletely characterized because most previous efforts relied on measurement of steady-state mRNAs. Here, we use nascent RNA sequencing to profile transcriptional dynamics of primary neuron cultures undergoing network activity shifts. We find pervasive transcriptional changes, in which ∼45% of expressed genes respond to network activity shifts. We further link retinoic acid-induced 1 (RAI1), the Smith-Magenis syndrome gene, to the transcriptional program driven by reduced network activity. Remarkable agreement among nascent transcriptomes, dynamic chromatin occupancy of RAI1, and electrophysiological properties of Rai1-deficient neurons demonstrates the essential roles of RAI1 in suppressing synaptic upscaling in the naive network, while promoting upscaling triggered by activity silencing. These results highlight the utility of bona fide transcription profiling to discover mechanisms of activity-dependent chromatin remodeling that underlie normal and pathological synaptic plasticity.

Keywords: Bru-seq; RAI1; Smith-Magenis Syndrome; activity-dependent transcription; chromatin regulation; nascent RNA; neurodevelopmental disorders; synaptic scaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Female
  • Humans
  • Male
  • Mice
  • Nerve Net / metabolism
  • Nerve Net / physiology
  • Neuronal Plasticity / physiology*
  • Prosencephalon / cytology
  • Prosencephalon / metabolism
  • Prosencephalon / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Synapses / genetics
  • Synapses / metabolism
  • Synapses / physiology*
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcriptional Activation


  • RAI1 protein, human
  • Rai1 protein, mouse
  • Trans-Activators
  • Transcription Factors