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

Didier Auboeuf, Dennis H. Dowhan, Yun Kyoung Kang, Kimberly Larkin, Jae Woon Lee, Susan M. Berget, Bert W. O'Malley

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2270-2274
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number8
DOIs
StatePublished - Feb 22 2004

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Differential recruitment of nuclear receptor coactivators may determine alternative RNA splice site choice in target genes'. Together they form a unique fingerprint.

Cite this