Structure and expression of two nuclear receptor genes in marsupials: insights into the evolution of the antisense overlap between the α-thyroid hormone receptor and Rev-erbα.
Structure and expression of two nuclear receptor genes in marsupials: insights into the evolution of the antisense overlap between the α-thyroid hormone receptor and Rev-erbα.
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DOI：
10.1186/1471-2199-11-97
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发表时间：
2010-12-10
影响因子：
--
通讯作者：
Munroe SH
中科院分区：
文献类型：
--
作者：
Rindfleisch BC;Brown MS;VandeBerg JL;Munroe SH
α-甲状腺激素受体（TRα、NR1A1）mRNA 的替代加工产生两种功能拮抗的核受体：TRα1（α 型受体）和 TRα2（一种仅在哺乳动物中发现的非激素结合变体）。 TRα2 与另一种核受体蛋白 Rev-erbα (NR1D1) 的 mRNA 具有不寻常的反义编码重叠。在本研究中，我们检查了灰短尾负鼠 Monodelphis Domestica 中这些基因的结构和表达，并与真兽类哺乳动物和其他三种有袋动物 Didelphis virginiana、Potorous tridactylus 和 Macropus eugenii 的结构和表达进行比较，以了解这种反义重叠的进化和调节作用。负鼠和真兽类哺乳动物中编码 TRα1 和 Rev-erbα 的 mRNA 的序列、表达和基因组结构非常相似。然而，对应于 TRα2 编码区的序列似乎被截短了近 100 个氨基酸。虽然 TRα1 和 Rev-erbα 的表达在 0 天至 18 周龄的家蝇的所有组织中都很容易检测到，但在所检查的任何组织或阶段中均未检测到 TRα2 mRNA。这些结果与 TRα2 在啮齿动物和其他真兽类哺乳动物中广泛且丰富的表达形成鲜明对比。为了检查 TRα mRNA 选择性剪接的要求，构建了一系列嵌合小基因。结果表明，负鼠 TRα2 特异性 5' 剪接位点序列完全能够进行剪接，但与 TRα2 3' 剪接位点同源的序列则不然，尽管有袋动物序列与大鼠中的核心剪接位点元件非常相似。我们的结果强烈表明，变异核受体亚型 TRα2 在有袋动物中不表达，因此 TRα 和 Rev-erbα 之间的反义重叠是真兽类哺乳动物所独有的。对有袋动物和真兽类物种中 TRα 和 Rev-erbα 基因的进一步研究有望进一步深入了解 TRα2 的生理功能以及与 Rev-erbα 相关的反义重叠在调节这些基因表达中的作用。
Alternative processing of α-thyroid hormone receptor (TRα, NR1A1) mRNAs gives rise to two functionally antagonistic nuclear receptors: TRα1, the α-type receptor, and TRα2, a non-hormone binding variant that is found only in mammals. TRα2 shares an unusual antisense coding overlap with mRNA for Rev-erbα (NR1D1), another nuclear receptor protein. In this study we examine the structure and expression of these genes in the gray short-tailed opossum, Monodelphis domestica, in comparison with that of eutherian mammals and three other marsupial species, Didelphis virginiana, Potorous tridactylus and Macropus eugenii, in order to understand the evolution and regulatory role of this antisense overlap. The sequence, expression and genomic organization of mRNAs encoding TRα1 and Rev-erbα are very similar in the opossum and eutherian mammals. However, the sequence corresponding to the TRα2 coding region appears truncated by almost 100 amino acids. While expression of TRα1 and Rev-erbα was readily detected in all tissues of M. domestica ages 0 days to 18 weeks, TRα2 mRNA was not detected in any tissue or stage examined. These results contrast with the widespread and abundant expression of TRα2 in rodents and other eutherian mammals. To examine requirements for alternative splicing of TRα mRNAs, a series of chimeric minigenes was constructed. Results show that the opossum TRα2-specific 5' splice site sequence is fully competent for splicing but the sequence homologous to the TRα2 3' splice site is not, even though the marsupial sequences are remarkably similar to core splice site elements in rat. Our results strongly suggest that the variant nuclear receptor isoform, TRα2, is not expressed in marsupials and that the antisense overlap between TRα and Rev-erbα thus is unique to eutherian mammals. Further investigation of the TRα and Rev-erbα genes in marsupial and eutherian species promises to yield additional insight into the physiological function of TRα2 and the role of the associated antisense overlap with Rev-erbα in regulating expression of these genes.
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影响因子：
64.8
作者：
Alenghat, Theresa;Meyers, Katherine;Mullican, Shannon E.;Leitner, Kirstin;Adeniji-Adele, Adetoun;Avila, Jacqueline;Bucan, Maja;Ahima, Rexford S.;Kaestner, Klaus H.;Lazar, Mitchell A.
通讯作者：
Lazar, Mitchell A.
影响因子：
56.9
作者：
Carninci, P;Kasukawa, T;Hayashizaki, Y
通讯作者：
Hayashizaki, Y
影响因子：
56.9
作者：
Kapranov, Philipp;Cheng, Jill;Gingeras, Thomas R.
通讯作者：
Gingeras, Thomas R.
DOI：
10.1016/0006-291x(92)90652-2
发表时间：
1992-04-30
影响因子：
3.1
作者：
JANNINI, EA;MITSUHASHI, T;NIKODEM, VM
通讯作者：
NIKODEM, VM
影响因子：
64.5
作者：
Bookout, Angie L.;Jeong, Yangsik;Mangelsdorf, David J.
通讯作者：
Mangelsdorf, David J.