Transcriptional Elongation Factor Elongin A Regulates Retinoic Acid-Induced Gene Expression during Neuronal Differentiation

Takashi Yasukawa, Shachi Bhatt, Tamotsu Takeuchi, Junya Kawauchi, Hidehisa Takahashi, Aya Tsutsui, Takuya Muraoka, Makoto Inoue, Masayuki Tsuda, Shigetaka Kitajima, Ronald C. Conaway, Joan W. Conaway, Paul A. Trainor, Teijiro Aso

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1129-1136
Number of pages8
JournalCell Reports
Volume2
Issue number5
DOIs
StatePublished - Nov 29 2012
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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