In the present study, we have explored the mechanism by which PARP1/RNA interactions regulated gene expression in HK-2 cells by obtaining PARP1-regulated transcriptomes using RNA-seq and iRIP (improved RNA immunoprecipitation)-seq. In the latter, doxorubicin-induced DNA damage and cytosolic ROS have been found to be mediated by PARP1 via independent pathways ], which prompted us to further investigate PARP1 targets and their regulatory role in HK-2 cells. In addition, PARP1 hyperactivity and elevation of intracellular Ca 2+ are responsible for the amplification of ROS-induced nonapoptotic cell death in HK-2 proximal tubular epithelial cells ]. In these, the renal disease presents itself with various degrees of renal proximal tubular epithelial cell injury. Moreover, PARP1 is associated with several types of renal diseases, such as renal failure ], renal cell carcinoma ], and renal ischemia–reperfusion injury ].
PARP1 was found to preferentially bind RNA-containing GC-rich sequences, and 20 484 sites were located in intron regions ]. Recently, a CLIP-seq study of PARP1 RNA targets in human HeLa cells identified an overlapping set of 22 142 PARP1 RNA-binding peaks mapped to mRNAs. PARP1 participates in regulation of the gene expression at both transcription initiation and pre-mRNA splicing levels by binding to RNA, splicing factors, and chromatin ]. Poly(ADP-ribose) polymerase 1 (PARP1) has been reported to be involved in RNA synthesis and transcription ], mRNA stability ], and variable splicing of RNA ]. RBPs bind to these target sequences forming ribonucleoprotein complexes ], which regulate transcription, pre-mRNA processing, and translation ]. To understand the regulatory roles of RBPs in gene expression, their RNA target sites must be identified. RNA-binding proteins (RBPs) are involved in the regulation of both physiological and pathological states ].
STRING, Search Tool for the retrieval of interacting genes RASGs, regulated alternative splicing genes
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