The Study Of The Mechanism Of PARP-1Involved In The MRNA Stability Of Post-transcriptional Regulation

Poly(ADP-ribose) polymerase (PARP)-1is a nuclear enzyme which is ubiquitous in eukaryotes, and it is the first characterized and the best known member of the PARP family.PARP-1is an enzyme that can be highly activated in response to DNA damage,whereby,polymers of ADP-ribose(PAR) are formed using NAD+as a substrate and covalently attached to a number of target proteins.The majority of research showed that PARP-1is an active participant in the transcription regulation of many genes.In eukaryotes, the process of gene expression is controlled by multiple levels, of which, post-transcriptional regulation has become a research focus. Post-transcription-al regulation include mRNA stability, location and translation efficiency, and mRNA decay plays a critical role in gene expression regulation. Many elements are involved in mRNA stability regulation, including the5’cap structure,3’poly (A) tail,5’untranslated region (5’untranslated region,5’UTR),3’untranslated region (3’untranslated region,3’UTR), etc.And most studies are focus on AU-rich element in the3’UTR (ARE) and the ARE-binding proteins. ARE elements are present in the3’UTRs of many cytokines and inflammatory factors.They can affect mRNA stability in the interaction with the corresponding ARE-binding proteins., enabling the translation and expression contol of inflammatory cytokines in the level of post-transcriptional, and greatly influenced inflammatory response process, but the exact mechanism is not clear. In addition, post-translational modifications of these ARE-binding proteins will also affect the stability of specific mRNA transcripts, such as phosphorylation.While the regulation of mRNA stability is an intricate process, related research of other modifications’s existence,which can affect these mRNA binding protein properties,is still very limited.At present,the research of PARP-1are most about its post-translational modification of proteins (poly (ADP-ribosyl) ation) and the level of transcription regulation. PARP-1is involved in the regulation of inflammatory genes mRNA stability in the level of post-transcriptional, but its mechanism remains to be further studied.As our studies show, PARP-1can affect IL-18gene expression by its3’UTR region as a cis-regulatory elements, and participate in LPS-induced cytokines MIP-2mRNA stability regulation,as well as together with the ARE-binding protein HuR. Our study will help us to further explore the mechanism of PARP-1regulates gene expression by the impact on the post-transcriptional regulation of mRNA stability.And we hope it can add new content to the epigenetic regulation mechanism.Otherwise, for Inflammatory disease that highly involved in post-transcriptional regulation inhibition of PARP-1activity may be a new treatment.