459 research outputs found

    Native Milwaukee

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    David Holmes, Timothy Barnard, And Questionable Loyalties

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    Structure and expression of two nuclear receptor genes in marsupials: insights into the evolution of the antisense overlap between the Ī±-thyroid hormone receptor and Rev-erbĪ±

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    <p>Abstract</p> <p>Background</p> <p>Alternative processing of Ī±-thyroid hormone receptor (TRĪ±, NR1A1) mRNAs gives rise to two functionally antagonistic nuclear receptors: TRĪ±1, the Ī±-type receptor, and TRĪ±2, a non-hormone binding variant that is found only in mammals. TRĪ±2 shares an unusual antisense coding overlap with mRNA for Rev-erbĪ± (NR1D1), another nuclear receptor protein. In this study we examine the structure and expression of these genes in the gray short-tailed opossum, <it>Monodelphis domestica</it>, in comparison with that of eutherian mammals and three other marsupial species, <it>Didelphis virginiana, Potorous tridactylus </it>and <it>Macropus eugenii</it>, in order to understand the evolution and regulatory role of this antisense overlap.</p> <p>Results</p> <p>The sequence, expression and genomic organization of mRNAs encoding TRĪ±1 and Rev-erbĪ± are very similar in the opossum and eutherian mammals. However, the sequence corresponding to the TRĪ±2 coding region appears truncated by almost 100 amino acids. While expression of TRĪ±1 and Rev-erbĪ± was readily detected in all tissues of <it>M. domestica </it>ages 0 days to 18 weeks, TRĪ±2 mRNA was not detected in any tissue or stage examined. These results contrast with the widespread and abundant expression of TRĪ±2 in rodents and other eutherian mammals. To examine requirements for alternative splicing of TRĪ± mRNAs, a series of chimeric minigenes was constructed. Results show that the opossum TRĪ±2-specific 5' splice site sequence is fully competent for splicing but the sequence homologous to the TRĪ±2 3' splice site is not, even though the marsupial sequences are remarkably similar to core splice site elements in rat.</p> <p>Conclusions</p> <p>Our results strongly suggest that the variant nuclear receptor isoform, TRĪ±2, is not expressed in marsupials and that the antisense overlap between TRĪ± and Rev-erbĪ± thus is unique to eutherian mammals. Further investigation of the TRĪ± and Rev-erbĪ± genes in marsupial and eutherian species promises to yield additional insight into the physiological function of TRĪ±2 and the role of the associated antisense overlap with Rev-erbĪ± in regulating expression of these genes.</p
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