The RNA binding protein YB-1 binds A/C-rich exon enhancers and stimulates splicing of the CD44 alternative exon v4

Stickeler, Elmar; Fraser, Sherri D.; Hönig, Arnd; Chen, Andy L.; Berget, Susan M.; Cooper, Thomas A.

doi:10.1093/emboj/20.14.3821

Cited by 182 publications

(181 citation statements)

References 56 publications

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“…Mouse mammary tumor virus (MMTV), progesterone (Pg)-responsive element (PRE)-, or estrogen-responsive element (ERE) 2 -TATA promoters were cloned upstream of the previously described CD44, fibronectin (FN), calcitonin͞CT gene-related peptide (CT͞CGRP), or adenovirus-based test genes (20)(21)(22)(23). The precise cloning steps are available on request.…”

Section: Methodsmentioning

confidence: 99%

“…To carry out the present study, we cloned different reporter genes, the products of which undergo various alternative splicing decisions, downstream of either the MMTV promoter or an ERE-TATA promoter sensitive to either Pg or E 2 , respectively. The first minigene tested was derived from the human CD44 gene that contains 21 exons, 11 of which can be alternatively spliced (20). The reporter gene described in Fig.…”

Section: Different Steroid Hormones Have Different Effects On Alternamentioning

confidence: 99%

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

Auboeuf

Dowhan

Kang

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

111

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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. G ene expression regulation is a multistep process, including the synthesis of the pre-mRNA or transcription; the 5Ј and 3Ј end maturation of the transcript or capping and polyadenylation, respectively; the removal of the introns from the premRNA; and the export to the cytosol of the mRNA and its translation (1). Steroid hormones play a major role in the control of cellular fate and cellular homeostasis by modulating the expression of genes, the products of which are involved in cellular programs such as apoptosis, proliferation, differentiation, and in cellular metabolism (2, 3). Most of the studies of steroid hormone action focus on transcriptional effects that are mediated by the binding of steroid hormone receptors to hormone response elements localized in target gene promoters (4). Nevertheless, the biological consequences resulting from the modulation of the transcriptional activity of genes cannot be precisely predicted because of alternative splicing. Approximately 60% of human pre-mRNAs undergo an alternative splicing process that results in the synthesis from one gene of different mRNAs encoding different proteins having different biological actions (5). For instance, the products of many genes involved in apoptosis are alternatively spliced and this splicingcan result in the synthesis of isoforms that antagonize each other by having pro-vs. antiapoptosis effects (6). Therefore, the alternative splicing process can change considerably the biological consequences resulting from the transcriptional modulation of steroid hormone target genes and an important question to address is the mechanis...

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Section: Methodsmentioning

confidence: 99%

Section: Different Steroid Hormones Have Different Effects On Alternamentioning

confidence: 99%

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

Auboeuf

Dowhan

Kang

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

111

View full text Add to dashboard Cite

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“…YB1 also stimulates RNA splicing from different templates (Raffetseder et al, 2003;Stickeler et al, 2001) and is a potent and general stabilizer of capped mRNA (Evdokimova et al, 2001). Thus, YB1 appears to have pleiotropic functions in transcription, RNA splicing and translation (Matsumoto and Wolffe, 1998;Sommerville, 1999).…”

Section: Introductionmentioning

confidence: 99%

Y-box factor YB1 controls p53 apoptotic function

et al. 2005

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Nuclear localization and high levels of the Y-box-binding protein YB1 appear to be important indicators of drug resistance and tumor prognosis. YB1 also interacts with the p53 tumor suppressor protein. In this paper, we have continued to explore YB1/p53 interactions. We report that transcriptionally active p53 is required for nuclear localization of YB1. We go on to show that nuclear YB1 regulates p53 function. Our data demonstrate that YB1 inhibits the ability of p53 to cause cell death and to transactivate cell death genes, but does not interfere with the ability of p53 to transactivate the CDKN1A gene, encoding the kinase p21 WAF1/CIP1 required for cell cycle arrest, nor the MDM2 gene. We also show that nuclear YB1 is associated with a failure to increase the level of the Bax protein in normal mammary epithelial cells after stress activation of p53. Together these data suggest that (nuclear) YB1 selectively alters p53 activity, which may in part provide an explanation for the correlation of nuclear YB1 with drug resistance and poor tumor prognosis.

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“…It is widely expressed across a broad range of tissues, but in vivo data on the biological function of YBX1 is limited because the Ybx1 null mouse is embryonic lethal [192,193]. YBX1 is as broad in its cellular function as in its expression, involved in transcription, translational control and splicing depending on the cell type expressing it and post-translational modifications [11,24,36,39,41,42,[48][49][50][51][193][194][195][196]. Perhaps because of its myriad cellular roles, there is little consistency about when developmentally it is expressed across tissues, or where inside the cell it is located, with it being reported in the nucleus, cytoplasm, or shuttling between the two based on posttranscriptional modifications [41,188,194,[196][197][198].…”

Section: Introductionmentioning

confidence: 99%

“…YBX1 has a broad range of reported functions including transcriptional regulation and splicing depending on the cell type expressing it and post-translational modifications [11,49,51,[193][194][195][196][197][198][199]212]. The other major function of YBX1 is in RNA translational control, generally through mRNA sequestration and prevention of transcript degradation, although some studies suggest that it can positively regulate translation as well [24, 36, 39-42, 45-48, 50, 52, 53].…”

Section: Introductionmentioning

confidence: 99%