Abstract 2051: Regulation of RNA processing by PADI4 pathway

Abstract

Abstract We recently reported that p53 regulated protein citrullination through the transcriptional regulation of PADI4 that converts an arginine residue in proteins to a citrulline residue. In response to DNA damage, p53-PADI4 pathway induced citrullination of NPM1, Histone H4, and Lamin C, and subsequently promoted apoptotic pathway. To elucidate entire roles of p53-PADI4 pathway, we screened novel targets by LC-MS analysis and found that majority of hnRNP family members are citrullinated by ectopic expression of PADI4. LC-MS analysis and specific antibody revealed citrullination of hnRNP G at arginine 223 residue. In addition, citrullination of hnRNP G inhibited interaction with RNA helicases or other hnRNP family members. Citrullination motif analysis revealed the enrichment of D, G, S, E, and A at -1 (56.0%), +1 (55.8%) and +2 (45.8%) position. Since hnRNP family is involved in RNA processing, we conducted RNA sequence analysis by using bone marrow from Padi4+/+ or Padi4-/- mice. As a result, Padi4 was shown to alter the splicing pattern of several genes. Moreover, Padi4-/-p53+/- mice exhibited significantly shorter survival time compared with Padi4+/+p53+/- mice. Our finding revealed a novel role of p53-PADI4 pathway in RNA splicing and human carcinogenesis. Citation Format: Chizu Tanikawa, Koji Ueda, Yusuke Nakamura, Koichi Matsuda. Regulation of RNA processing by PADI4 pathway. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2051. doi:10.1158/1538-7445.AM2015-2051