Multiomics analysis of the NAD⁺-PARP1 axis reveals a role for site-specific ADP-ribosylation in splicing in embryonic stem cells.

ABSTRACT: The differentiation of embryonic stem cells (ESCs) into a lineage-committed state is a dynamic process involving changes in cellular metabolism, epigenetic modifications, post-translational modifications, gene expression, and RNA processing. Here we integrated data from metabolomic, proteomic, and transcriptomic assays to characterize how alterations in NAD⁺ metabolism during the differentiation of mouse ESCs lead to alteration of the PARP1-mediated ADP-ribosylated (ADPRylated) proteome and mRNA isoform specialization. Our metabolomic analyses indicate that mESCs use distinct NAD⁺ biosynthetic pathways in different cell states: the de novo pathway in the pluripotent state, and the salvage and Preiss-Handler pathways as differentiation progresses. We observed a dramati

SUBMITTER: Jones A 

PROVIDER: S-EPMC9186393 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature