Role of poly(ADP-ribose) polymerase 1 in regulating RNA polymerase II elongation and mRNA splicing

Grants and Contracts Details


Alternative splicing occurs co-transcriptionally and is mediated by chromatin structure. We recently showed that PARP1-chromatin binding regulates AS, however the mechanism by which it does so is not clearly defined. We proposed two non-mutually exclusive models: 1) PARP1 act as an adapter, binding to chromatin and bridging RNAPII and its associated splicing factors (SFs) close to RNA and/or 2) PARP1- chromatin structure modulates the rate of RNAPII elongation, allowing enough resident time for RNAPII and its associated SFs to recognize specific splice sites. We have shown that PARP1-chromatin structure modulates RNAPII kinetics, though the mechanism is unknown. We propose to investigate the mechanisms by which PARP1 modulates RNAPII elongation either through its chromatin binding and/or whether PARP1’s binding to nascent mRNAs impacts the optimal rate of RNAPII critical for splicing. To complete this project, we propose two aims: 1) to determine the mechanism by which PARP1 modulates the rate of optimal RNAPII elongation to rive alternative splicing decisions and 2) whether its binding to RNA impacts alternative splicing and RNA biogenesis. These studies will provide a platform determine the mechanism by which PARP1 recognizes and is recruited to specific regions to drive specific splicing decisions. Additionally it provide a platform to begin to study how PARP1 modulates gene expression, especially at the initiation, splicing, export and decay processes.
Effective start/end date8/15/201/3/22


  • National Science Foundation: $780,000.00


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