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The Involvement of Splicing Factor hn RNP A1 in UVB ‐induced Alternative Splicing of hdm2
Author(s) -
Feng Jianguo,
Li Li,
Tong Lingying,
Tang Liling,
Wu Shiyong
Publication year - 2016
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.12564
Subject(s) - rna splicing , splicing factor , sr protein , alternative splicing , protein splicing , heterogeneous nuclear ribonucleoprotein , exonic splicing enhancer , ribonucleoprotein , biology , rna binding protein , messenger rna , microbiology and biotechnology , chemistry , biochemistry , gene , rna
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 (hn RNP ) A1 and serine/arginine‐rich splicing factor 1 ( SRSF 1), in regulating UVB ‐induced hdm2 splicing. Our study indicated that while the expression of both hn RNP A1 and SRSF 1 are induced, only hn RNP A1 is involved in hdm2 alternative splicing upon UVB irradiation. Overexpression of hn RNP A1 resulted in decrease of full‐length hdm2 (hdm2‐ FL ) and increase of hdm2B, one of hdm2 alternate‐splicing forms; while down‐regulated hn RNP 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 hn RNP A1 to hdm2 pre‐ mRNA . In conclusion, we elucidated that UVB induces alternative splicing of hdm2 by increasing the expression and the binding of hn RNP A1 to hdm2 full‐length mRNA .