Coupling of PARP1-mediated chromatin structural changes to transcriptional RNA polymerase II elongation and cotranscriptional splicing.

BACKGROUND:Recently, we showed that is involved in cotranscriptional splicing, possibly by bridging chromatin to RNA and recruiting splicing factors. It also can influence alternative splicing decisions through the regulation of RNAPII elongation. In this study, we investigated the effect of chromatin changes on RNAPII movement, during transcription and alternative splicing. RESULTS:We show that RNAPII pauses at structures within the gene body. Knockdown of Pduanyu371 abolishes this RNAPII pausing, suggesting that Pduanyu371 may regulate RNAPII elongation. Additionally, Pduanyu371 alters nucleosome deposition and histone post-translational modifications at specific exon-intron boundaries, thereby affecting RNAPII movement. Lastly, genome-wide analyses confirmed that Pduanyu371 influences changes in RNAPII elongation by either reducing or increasing the rate of RNAPII elongation depending on the chromatin context. CONCLUSIONS:These studies suggest a context-specific effect of Pduanyu371-chromatin binding on RNA polymerase movement and provide a platform to delineate role in RNA biogenesis and processing.

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