title: The Involvement of Splicing Factor hnRNP A1 in UVB-induced Alternative Splicing of hdm2.
abstract: Human homolog double minute 2 (hdm2), an oncoprotein, which binds to tumor suppressor p53 to facilitate its degradation, has been known to contribute to tumorigenesis. Its splicing variants are reported to be highly expressed in many cancers and can be induced by ultraviolet B light (UVB). However, the mechanisms of how UVB radiation induces hdm2 alternative splicing still remain unclear. In this study, we investigated the roles of two common splicing factors, heterogeneous nuclear ribonucleoproteins (hnRNP) A1 and serine/arginine-rich splicing factor 1 (SRSF1), in regulating UVB-induced hdm2 splicing. Our study indicated that while the expression of both hnRNP A1 and SRSF1 are induced, only hnRNP A1 is involved in hdm2 alternative splicing upon UVB irradiation. Overexpression of hnRNP A1 resulted in decrease of full-length hdm2 (hdm2-FL) and increase of hdm2B, one of hdm2 alternate-splicing forms; while down-regulated hnRNP A1 expression led to the decrease of the hdm2-FL and hdm2B in HaCaT cells. Protein-mRNA binding assay confirmed that UVB irradiation could increase the binding of hnRNP A1 to hdm2 pre-mRNA. In conclusion, we elucidated that UVB induces alternative splicing of hdm2 by increasing the expression and the binding of hnRNP A1 to hdm2 full-length mRNA.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.|Department of Chemistry and Biochemistry, Edison Biotechnology Institute, Ohio University, Athens, OH.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Feng
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Chemistry and Biochemistry, Edison Biotechnology Institute, Ohio University, Athens, OH.
authors.forename: Lingying
authors.initials: L
authors.lastname: Tong
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Chemistry and Biochemistry, Edison Biotechnology Institute, Ohio University, Athens, OH.
authors.forename: Shiyong
authors.identifier: 0000-0002-4104-4160
authors.initials: S
authors.lastname: Wu
mesh_terms: D017398:Alternative Splicing / Q000528:radiation effects*; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000068103:Serine-Arginine Splicing Factors / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; C000595779:SRSF1 protein, human; D000068103:Serine-Arginine Splicing Factors; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2