PARP1-mediated PARylation activity is essential for oligodendroglial differentiation and CNS myelination

Yan Wang, Yanhong Zhang, Sheng Zhang, Bokyung Kim, Vanessa L. Hull, Jie Xu, Preeti Prabhu, Maria Gregory, Veronica Martinez-Cerdeno, Xinhua Zhan, Wenbin Deng, Fuzheng Guo

Research output: Contribution to journalArticlepeer-review

Abstract

The function of poly(ADP-ribosyl) polymerase 1 (PARP1) in myelination and remyelination of the central nervous system (CNS) remains enigmatic. Here, we report that PARP1 is an intrinsic driver for oligodendroglial development and myelination. Genetic PARP1 depletion impairs the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes and impedes CNS myelination. Mechanistically, PARP1-mediated PARylation activity is not only necessary but also sufficient for OPC differentiation. At the molecular level, we identify the RNA-binding protein Myef2 as a PARylated target, which controls OPC differentiation through the PARylation-modulated derepression of myelin protein expression. Furthermore, PARP1's enzymatic activity is necessary for oligodendrocyte and myelin regeneration after demyelination. Together, our findings suggest that PARP1-mediated PARylation activity may be a potential therapeutic target for promoting OPC differentiation and remyelination in neurological disorders characterized by arrested OPC differentiation and remyelination failure such as multiple sclerosis.

Original languageEnglish (US)
Article number109695
JournalCell Reports
Volume37
Issue number1
DOIs
StatePublished - Oct 5 2021

Keywords

  • demyelination
  • multiple sclerosis
  • myelination
  • oligodendrocyte progenitor cells (OPCs)
  • oligodendrocytes (OLs)
  • OPC differentiation
  • PARG
  • PARP1
  • PARylation
  • remyelination

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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