Involvement of PARP1 in the regulation of alternative splicing

Elena Matveeva, John Maiorano, Qingyang Zhang, Abdallah M. Eteleeb, Paolo Convertini, Jing Chen, Vittoria Infantino, Stefan Stamm, Jiping Wang, Eric C. Rouchka, Yvonne N. Fondufe-Mittendorf*

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Specialized chromatin structures such as nucleosomes with specific histone modifications decorate exons in eukaryotic genomes, suggesting a functional connection between chromatin organization and the regulation of pre-mRNA splicing. Through profiling the functional location of Poly (ADP) ribose polymerase, we observed that it is associated with the nucleosomes at exon/intron boundaries of specific genes, suggestive of a role for this enzyme in alternative splicing. Poly (ADP) ribose polymerase has previously been implicated in the PARylation of splicing factors as well as regulation of the histone modification H3K4me3, a mark critical for co-transcriptional splicing. In light of these studies, we hypothesized that interaction of the chromatin-modifying factor, Poly (ADP) ribose polymerase with nucleosomal structures at exon-intron boundaries, might regulate pre-mRNA splicing. Using genome-wide approaches validated by gene-specific assays, we show that depletion of PARP1 or inhibition of its PARylation activity results in changes in alternative splicing of a specific subset of genes. Furthermore, we observed that PARP1 bound to RNA, splicing factors and chromatin, suggesting that Poly (ADP) ribose polymerase serves as a gene regulatory hub to facilitate co-transcriptional splicing. These studies add another function to the multi-functional protein, Poly (ADP) ribose polymerase, and provide a platform for further investigation of this protein's function in organizing chromatin during gene regulatory processes.

Original languageEnglish (US)
Article number15046
JournalCell Discovery
Volume2
DOIs
StatePublished - Feb 16 2016

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Keywords

  • Epigenetics
  • PARP1
  • chromatin
  • cotranscriptional splicing
  • gene regulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Matveeva, E., Maiorano, J., Zhang, Q., Eteleeb, A. M., Convertini, P., Chen, J., Infantino, V., Stamm, S., Wang, J., Rouchka, E. C., & Fondufe-Mittendorf, Y. N. (2016). Involvement of PARP1 in the regulation of alternative splicing. Cell Discovery, 2, [15046]. https://doi.org/10.1038/celldisc.2015.46