Arsenic Induces Polyadenylation of Canonical Histone mRNA by Down-regulating Stem-Loop-binding Protein Gene Expression
| Autor: | Hsiang-Chi Tseng, Max Costa, Magdy Shamy, Da-Zhong Xu, Kathrin Kiok, Hong Sun, Jason Brocato, Lei Fang, Danqi Chen, Chunyuan Jin, Yana Chervona |
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| Rok vydání: | 2014 |
| Předmět: |
Polyadenylation
Mitosis Biology Biochemistry Chromosomes Arsenic Epigenesis Genetic S Phase Histones Cell Line Tumor Gene expression Histone H2A Humans RNA Messenger Epigenetics Molecular Biology mRNA Cleavage and Polyadenylation Factors Regulation of gene expression SLBP Nuclear Proteins Cell Biology Molecular biology HEK293 Cells Histone Gene Expression Regulation Histone methyltransferase Leukocytes Mononuclear biology.protein DNA Damage Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 289:31751-31764 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m114.591883 |
| Popis: | The replication-dependent histone genes are the only metazoan genes whose messenger RNA (mRNA) does not terminate with a poly(A) tail at the 3'-end. Instead, the histone mRNAs display a stem-loop structure at their 3'-end. Stem-loop-binding protein (SLBP) binds the stem-loop and regulates canonical histone mRNA metabolism. Here we report that exposure to arsenic, a carcinogenic metal, decreased cellular levels of SLBP by inducing its proteasomal degradation and inhibiting SLBP transcription via epigenetic mechanisms. Notably, arsenic exposure dramatically increased polyadenylation of canonical histone H3.1 mRNA possibly through down-regulation of SLBP expression. The polyadenylated H3.1 mRNA induced by arsenic was not susceptible to normal degradation that occurs at the end of S phase, resulting in continued presence into mitosis, increased total H3.1 mRNA, and increased H3 protein levels. Excess expression of canonical histones have been shown to increase sensitivity to DNA damage as well as increase the frequency of missing chromosomes and induce genomic instability. Thus, polyadenylation of canonical histone mRNA following arsenic exposure may contribute to arsenic-induced carcinogenesis. |
| Databáze: | OpenAIRE |
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