An Investigation into the Novel Role of PARP1 in Co-transcriptional Splicing

The importance of RNA and chromatin in the multiple levels of regulation that ensure proper functioning of the eukaryotic transcriptome and proteome has been increasingly recognized in recent years. Converging lines of evidence show that these processes are more interrelated than previously thought and that there is continuous feed-forward crosstalk among the processes of chromatin organization, transcription, and pre-mRNA splicing. Indeed it is now known that there are multiple layers of regulation that function jointly to organize chromatin, with consequences for proper transcription and RNA processing. While it is known how chromatin structure regulates transcription, very little is known of how the chromatin structure regulates mRNA processing. Intriguing results from several recent studies show that transcription and splicing are co-regulated and that chromatin structure plays a crucial role in this process. These data suggest that factors that modulate the chromatin structure are likely important in co-transcriptional regulation. In fact, recent discovery of the laboratory that PARP-1, a chromatin architectural protein involved in transcriptional regulation, also fine-tunes alternative splicing events, adds an additional layer to our understanding of chromatin structural dynamics in gene regulation (transcription and splicing). This function of PARP-1 is novel and exciting but a better understanding of the mechanism by which PARP-1 modulates pre-mRNA splicing is needed. Such an understanding will provide critical insights into the role of PARP-1 in modulating chromatin structural dynamics to affect changes in gene regulation.