Transcriptional elongation factor elongin A regulates retinoic acid-induced gene expression during neuronal differentiation

Cell Rep. 2012 Nov 29;2(5):1129-36. doi: 10.1016/j.celrep.2012.09.031. Epub 2012 Nov 1.


Elongin A increases the rate of RNA polymerase II (pol II) transcript elongation by suppressing transient pausing by the enzyme. Elongin A also acts as a component of a cullin-RING ligase that can target stalled pol II for ubiquitylation and proteasome-dependent degradation. It is not known whether these activities of Elongin A are functionally interdependent in vivo. Here, we demonstrate that Elongin A-deficient (Elongin A(-/-)) embryos exhibit abnormalities in the formation of both cranial and spinal nerves and that Elongin A(-/-) embryonic stem cells (ESCs) show a markedly decreased capacity to differentiate into neurons. Moreover, we identify Elongin A mutations that selectively inactivate one or the other of the aforementioned activities and show that mutants that retain the elongation stimulatory, but not pol II ubiquitylation, activity of Elongin A rescue neuronal differentiation and support retinoic acid-induced upregulation of a subset of neurogenesis-related genes in Elongin A(-/-) ESCs.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / drug effects*
  • Cell Line
  • Elongin
  • Embryo, Mammalian / metabolism
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Gene Expression Regulation / drug effects
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Neurons / cytology
  • Neurons / metabolism*
  • RNA Polymerase II / metabolism
  • Sequence Alignment
  • Transcription Elongation, Genetic
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tretinoin / pharmacology*
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination


  • Eloa protein, mouse
  • Elongin
  • Transcription Factors
  • Tretinoin
  • Ubiquitin-Protein Ligases
  • RNA Polymerase II
  • Rpb1 protein, mouse

Associated data

  • GEO/GSE30911