Rivers, C, Flynn, A, Qian, X et al. (4 more authors) (2009) Characterization of Conserved Tandem Donor Sites and Intronic Motifs Required for Alternative Splicing in Corticosteroid Receptor Genes. Endocrinology, 150 (11). pp. 4958-4967. ISSN 0013-7227
Abstract
Alternative splicing events from tandem donor sites result in mRNA variants coding for additional amino acids in the DNA binding domain of both the glucocorticoid (GR) and mineralocorticoid (MR) receptors. We now show that expression of both splice variants is extensively conserved in mammalian species, providing strong evidence for their functional significance. An exception to the conservation of the MR tandem splice site (an A at position +5 of the MR+12 donor site in the mouse) was predicted to decrease U1 small nuclear RNA binding. In accord with this prediction, we were unable to detect the MR+12 variant in this species. The one exception to the conservation of the GR tandem splice site, an A at position +3 of the platypus GRγ donor site that was predicted to enhance binding of U1 snRNA, was unexpectedly associated with decreased expression of the variant from the endogenous gene as well as a minigene. An intronic pyrimidine motif present in both GR and MR genes was found to be critical for usage of the downstream donor site, and overexpression of TIA1/TIAL1 RNA binding proteins, which are known to bind such motifs, led to a marked increase in the proportion of GRγ and MR+12. These results provide striking evidence for conservation of a complex splicing mechanism that involves processes other than stochastic spliceosome binding and identify a mechanism that would allow regulation of variant expression.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cancer and Pathology (LICAP) > Infection and Immunity (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 22 Aug 2019 10:56 |
Last Modified: | 22 Aug 2019 10:56 |
Status: | Published |
Publisher: | Oxford University Press |
Identification Number: | 10.1210/en.2009-0346 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:99703 |