An exonic splicing enhancer within a bidirectional coding sequence regulates alternative splicing of an antisense mRNA.
An exonic splicing enhancer within a bidirectional coding sequence regulates alternative splicing of an antisense mRNA.
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DOI：
10.4161/rna.7.2.11182
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发表时间：
2010-03
期刊：
影响因子：
4.1
通讯作者：
Munroe SH
中科院分区：
文献类型：
--
作者：
Salato VK;Rediske NW;Zhang C;Hastings ML;Munroe SH
越来越多的基因重叠序列的发现突出了在约束多个基因调控元件的背景下表达的问题。本研究确定了包含在两个基因中的调控序列，它们在3 '端以反义方向重叠。这些基因编码α-甲状腺激素受体基因（TRα或NR1A1）和Rev-erbα (NR1D1)。在哺乳动物中，TRα前mrna可选择性剪接产生编码功能性拮抗蛋白的mrna: TRα1，一种真正的甲状腺激素受体；和TRα2，一种非激素结合的变体，起到抑制作用。tr α2特异性剪接需要两个与Rev-erbα序列重叠的调控元件。这些元件的功能映射揭示了在重叠Rev-erbα序列的约束下进化的最小剪接增强元件。这些结果为双向编码序列中调控元件的进化提供了深入的见解。他们还展示了遗传密码在给定序列中容纳多层信息的能力，这是最近在理论基础上提出的密码的一个重要特性。
The discovery of increasing numbers of genes with overlapping sequences highlights the problem of expression in the context of constraining regulatory elements from more than one gene. This study identifies regulatory sequences encompassed within two genes that overlap in an antisense orientation at their 3′ ends. The genes encode the α-thyroid hormone receptor gene (TRα or NR1A1) and Rev-erbα (NR1D1). In mammals TRα pre-mRNAs are alternatively spliced to yield mRNAs encoding functionally antagonistic proteins: TRα1, an authentic thyroid hormone receptor; and TRα2, a non-hormone-binding variant that acts as a repressor. TRα2-specific splicing requires two regulatory elements that overlap with Rev-erbα sequences. Functional mapping of these elements reveals minimal splicing enhancer elements that have evolved within the constraints of the overlapping Rev-erbα sequence. These results provide insight into the evolution of regulatory elements within the context of bidirectional coding sequences. They also demonstrate the ability of the genetic code to accommodate multiple layers of information within a given sequence, an important property of the code recently suggested on theoretical grounds.
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