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Alternative splicing in exon 9 of glucocorticoid receptor pre-mRNA is regulated by SRp40

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Abstract

Increasing evidence indicates that alternative splicing of human glucocorticoid receptor (GR) transcripts is implicated in the development of glucocorticoid resistance but the underlying mechanism was not well known. Serine/arginine-rich (SR) proteins and heterogeneous nuclear ribonucleoprotein (hnRNP) A1 play an important role in the spliceosome assembly. In this study, we analyzed the effects of different SR proteins and hnRNP A1 on the alternative splicing of GR pre-mRNA in HeLa and 293T cells using a minigene transfection assay. Our results revealed that only SRp40 could induce a GRα to GRβ shift of pre-mRNA splicing in exon 9 in HeLa cells and this effect induced by SRp40 was further confirmed by small interfering RNA study. However, in 293T cells, SRp40 could not induce this shift. These results indicated that SRp40 may influence the alternative splicing of GR pre-mRNA to regulate the ratio of GRα to GRβ, and this effect is cell-dependent.

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Acknowledgments

We showed our great thanks to Professor Francisco E. Baralle (International Centre for Genetic Engineering and Biotechnology, Trieste, Italy) for providing hnRNPA1 and SR constructs. This work was supported by the Nature Science Foundation of China (30670936).

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Authors and Affiliations

  1. Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, 230022, Hefei, Anhui, China

    Xue-Bo Yan, Chen-Hong Tang, Yan Huang & Rong-Yu Liu

  2. Department of Neurobiology and Biophysics, School of Life Science, University of Science and Technology of China, 230027, Hefei, Anhui, China

    Xue-Bo Yan, Hui Fang, Zhi-Qiang Yu & Li-Min Wu

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  1. Xue-Bo Yan
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  2. Chen-Hong Tang
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  3. Yan Huang
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  7. Rong-Yu Liu
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Correspondence to Rong-Yu Liu.

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Yan, XB., Tang, CH., Huang, Y. et al. Alternative splicing in exon 9 of glucocorticoid receptor pre-mRNA is regulated by SRp40. Mol Biol Rep 37, 1427–1433 (2010). https://doi.org/10.1007/s11033-009-9529-z

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  • DOI: https://doi.org/10.1007/s11033-009-9529-z

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