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• W2107637402 abstract "Alternative pre-mRNA splicing is a major mechanism utilized by eukaryotic organisms to expand their protein-coding capacity. To examine the role of cell signaling in regulating alternative splicing, we analyzed the splicing of the Drosophila melanogaster TAF1 pre-mRNA. TAF1 encodes a subunit of TFIID, which is broadly required for RNA polymerase II transcription. We demonstrate that TAF1 alternative splicing generates four mRNAs, TAF1-1, TAF1-2, TAF1-3, and TAF1-4, of which TAF1-2 and TAF1-4 encode proteins that directly bind DNA through AT hooks. TAF1 alternative splicing was regulated in a tissue-specific manner and in response to DNA damage induced by ionizing radiation or camptothecin. Pharmacological inhibitors and RNA interference were used to demonstrate that ionizing-radiation-induced upregulation of TAF1-3 and TAF1-4 splicing in S2 cells was mediated by the ATM (ataxia-telangiectasia mutated) DNA damage response kinase and checkpoint kinase 2 (CHK2), a known ATM substrate. Similarly, camptothecin-induced upregulation of TAF1-3 and TAF1-4 splicing was mediated by ATR (ATM-RAD3 related) and CHK1. These findings suggest that inducible TAF1 alternative splicing is a mechanism to regulate transcription in response to developmental or DNA damage signals and provide the first evidence that the ATM/CHK2 and ATR/CHK1 signaling pathways control gene expression by regulating alternative splicing." @default.
• W2107637402 created "2016-06-24" @default.
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• W2107637402 creator A5051599630 @default.
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• W2107637402 date "2006-12-01" @default.
• W2107637402 modified "2023-10-15" @default.
• W2107637402 title "ATM and ATR Pathways Signal Alternative Splicing of <i>Drosophila TAF1</i> Pre-mRNA in Response to DNA Damage" @default.
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• W2107637402 doi "https://doi.org/10.1128/mcb.01125-06" @default.
• W2107637402 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1698527" @default.
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