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

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 regenera

SUBMITTER: Wang Y 

PROVIDER: S-EPMC9586836 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature