Differential recruitment of nuclear receptor coactivators may determine alternative RNA splice site choice in target genes.
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.
Auboeuf
Didier
D
Department of Molecular and Cellular Biology, Division of Diabetes, Endocrinology, and Metabolism, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Dowhan
Dennis H
DH
Kang
Yun Kyoung
YK
Larkin
Kimberly
K
Lee
Jae Woon
JW
Berget
Susan M
SM
O'Malley
Bert W
BW
D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics; D005091:Exons; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000235:genetics; D006728:Hormones / Q000502:physiology; D018960:Hyaluronan Receptors / Q000235:genetics; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D013256:Steroids / Q000502:physiology; D014158:Transcription, Genetic
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006728:Hormones; D018960:Hyaluronan Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D013256:Steroids; D015740:Calcitonin Gene-Related Peptide