Unknown

Dataset Information

0

ATM and ATR pathways signal alternative splicing of Drosophila TAF1 pre-mRNA in response to DNA damage.


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.

SUBMITTER: Katzenberger RJ 

PROVIDER: S-EPMC1698527 | biostudies-literature | 2006 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

ATM and ATR pathways signal alternative splicing of Drosophila TAF1 pre-mRNA in response to DNA damage.

Katzenberger Rebeccah J RJ   Marengo Matthew S MS   Wassarman David A DA  

Molecular and cellular biology 20061009 24


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 enc  ...[more]

Similar Datasets

| S-EPMC2491473 | biostudies-literature
| S-EPMC10651857 | biostudies-literature
| S-EPMC7198525 | biostudies-literature
| S-EPMC4716994 | biostudies-literature
| S-EPMC4526142 | biostudies-literature
| S-EPMC1461822 | biostudies-other
| S-EPMC3500379 | biostudies-literature
| S-EPMC2665233 | biostudies-literature
| S-EPMC6028976 | biostudies-literature
| S-EPMC7003074 | biostudies-literature