Distinct functions of acj6 splice forms in odor receptor gene choice.
Distinct functions of acj6 splice forms in odor receptor gene choice.
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DOI：
10.1523/jneurosci.6292-09.2010
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发表时间：
2010-04-07
期刊：
影响因子：
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通讯作者：
Carlson JR
中科院分区：
文献类型：
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作者：
Bai L;Carlson JR
单个嗅觉受体神经元（ORN）选择性地表达大量受体库中的一种或少数气味受体。气味受体的表达决定了 ORN 的气味反应谱。受体基因选择的过程部分依赖于转录因子的组合代码。在果蝇中，POU 结构域转录因子 Acj6 是转录因子代码的元素之一。在 acj6 无效突变体中，许多 ORN 不表达适当的气味受体基因，因此未正确指定。我们发现 acj6 被选择性剪接以在嗅觉器官中产生许多结构不同的转录本。我们生成在 acj6− 背景中表达 acj6 单剪接形式的果蝇。我们发现不同的剪接形式在功能上是不同的；它们指定 ORN 身份的能力有所不同。某些单独的剪接形式可以完全挽救某些 ORN 的规范。单个剪接形式可以在受体基因调节中发挥积极和消极的作用。 ORN 对拼接形式的要求有所不同；有些 ORN 不能被任何测试的单一剪接形式完全拯救，这表明某些 ORN 可能需要多种剪接形式的组合作用。一些 acj6 剪接形式的后期表达足以挽救一些 ORN 类别，这与 Acj6 亚型在受体基因表达中的直接作用一致。结果表明，选择性剪接可能会为气味受体基因选择过程中的调控代码增添另一层丰富性。
Individual olfactory receptor neurons (ORNs) selectively express one or a small number of odor receptors from among a large receptor repertoire. The expression of an odor receptor dictates the odor response spectrum of the ORN. The process of receptor gene choice relies in part on a combinatorial code of transcription factors. In Drosophila, the POU domain transcription factor Acj6 is one element of the transcription factor code. In acj6 null mutants, many ORNs do not express an appropriate odor receptor gene and thus are not correctly specified. We find that acj6 is alternatively spliced to yield many structurally distinct transcripts in the olfactory organs. We generate flies that express single splice forms of acj6 in an acj6− background. We find that different splice forms are functionally distinct; they differ in their abilities to specify ORN identities. Some individual splice forms can fully rescue the specification of some ORNs. Individual splice forms can function both positively and negatively in receptor gene regulation. ORNs differ in their requirements for splice forms; some are not fully rescued by any single splice form tested, suggesting that some ORNs may require the combinatorial action of multiple splice forms. Late expression of some acj6 splice forms is sufficient to rescue some ORN classes, consistent with a direct role for Acj6 isoforms in receptor gene expression. The results indicate that alternative splicing may add another level of richness to the regulatory code that underlies the process of odor receptor gene choice.