Differential recruitment of nuclear receptor coactivators may determine alternative RNA splice site choice in target genes

Auboeuft, Didier, Dowhan, Dennis H., Kang, Yun Kyoung, Larkin, Kimberly, Lee, Jae Woon, Berget, Susan M. and O'Malley, Bert W. (2004) Differential recruitment of nuclear receptor coactivators may determine alternative RNA splice site choice in target genes. Proceedings of The National Academy of Sciences of The United States of America, 101 8: 2270-2274. doi:10.1073/pnas.0308133100


Author Auboeuft, Didier
Dowhan, Dennis H.
Kang, Yun Kyoung
Larkin, Kimberly
Lee, Jae Woon
Berget, Susan M.
O'Malley, Bert W.
Title Differential recruitment of nuclear receptor coactivators may determine alternative RNA splice site choice in target genes
Journal name Proceedings of The National Academy of Sciences of The United States of America   Check publisher's open access policy
ISSN 0027-8424
Publication date 2004-02-24
Sub-type Article (original research)
DOI 10.1073/pnas.0308133100
Open Access Status Not Open Access
Volume 101
Issue 8
Start page 2270
End page 2274
Total pages 5
Place of publication Washington, D.C.
Publisher National Academy of Sciences of the U.S.
Language eng
Abstract The biological consequences of steroid hormone-mediated transcriptional activation of target genes might be difficult to predict because alternative splicing of a single neosynthesized precursor RNA can result in production of different protein isoforms with opposite biological activities. Therefore, an important question to address is the manner in which steroid hormones affect the splicing of their target gene transcripts. In this report, we demonstrate that individual steroid hormones had different and opposite effects on alternative splicing decisions, stimulating the production of different spliced variants produced from genes driven by steroid hormone-dependent promoters. Steroid hormone transcriptional effects are mediated by steroid hormone receptor coregulators that also modify alternative splicing decisions. Our data suggest that activated steroid hormone receptors recruit coregulators to the target promoter that participate in both the production and the splicing of the target gene transcripts. Because different coregulators activating transcription can have opposite effects on alternative splicing decisions, we conclude that the precise nature of the transcriptional coregulators recruited by activated steroid receptors, depending on the promoter and cellular contexts, may play a major role in regulating the nature of the spliced variants produced from certain target genes in response to steroid hormones.
Keyword Multidisciplinary Sciences
Breast-cancer Cells
In-vivo
Combinatorial Control
Hormone Receptors
Expression
Protein
Transcription
Coregulators
Isoforms
Asc-2
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: Excellence in Research Australia (ERA) - Collection
 
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Created: Wed, 17 Oct 2007, 22:42:46 EST