Alternative splicing and nonsense-mediated mRNA decay enforce neural specific gene expression.
Alternative splicing and nonsense-mediated mRNA decay enforce neural specific gene expression.
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DOI：
10.1016/j.ijdevneu.2016.03.003
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发表时间：
2016-12
期刊：
影响因子：
--
通讯作者：
Zheng S
中科院分区：
文献类型：
--
作者：
Zheng S
选择性前mrna剪接是大多数哺乳动物多外显子基因增加蛋白质组多样性的基本调控过程。无义介导的mRNA衰变（NMD）是一种保守的mRNA监测机制，可减轻基因突变或转录错误引起的有害影响。选择性剪接和NMD （AS-NMD）耦合，其中选择性剪接在翻译和NMD亚型之间切换，导致整体基因表达的微调，进而扩展这两个转录后调控过程的功能活动。AS-NMD以维持许多rna结合蛋白的稳态表达而闻名。我们进一步表明，AS-NMD是哺乳动物诱导突触支架蛋白PSD-95发育表达的保守机制。通过比较Psd-95及其祖先同源基因序列，我们发现AS-NMD对哺乳动物Psd-95的调控是一种选择压力的产物，它可以增强哺乳动物Psd-95蛋白的神经特异性表达。Psd-95的无脊椎同源物不受AS-NMD的调控，其蛋白产物不表现出神经特异性表达。考虑到哺乳动物神经系统中选择性剪接调控的普遍存在，AS-NMD可以以类似的方式控制许多其他基因的神经特异性表达。我们讨论了这些发现的意义，以及在推广as - nmd的调节和功能活性方面的挑战。
Alternative pre-mRNA splicing is a fundamental regulatory process for most mammalian multi-exon genes to increase proteome diversity. Nonsense-mediated mRNA decay (NMD) is a conserved mRNA surveillance mechanism to mitigate deleterious effects caused by gene mutations or transcriptional errors. Coupling alternative splicing and NMD (AS-NMD), in which alternative splicing switches between translational and NMD isoforms, results in fine-tuning overall gene expression to, in turn, expand the functional activities of these two post-transcriptional regulatory processes. AS-NMD is known for maintaining homeostatic expression of many RNA-binding proteins. We further show that AS-NMD is a conserved mechanism among mammals to induce developmental expression of the synaptic scaffold protein PSD-95. Comparing gene sequences between Psd-95 and its ancestral orthologues indicates that AS-NMD regulation of mammalian Psd-95 is a product of selective pressure and that it enforces neural-specific expression of PSD-95 proteins in mammals. Invertebrate homolog of Psd-95 is not subjected to AS-NMD regulation and its protein product does not exhibit neural-specific expression. Given the prevalence of alternative splicing regulation in the mammalian nervous system, neural-specific expression of many other genes could be controlled by AS-NMD in a similar manner. We discuss the implication of these discoveries, as well as the challenges in generalizing the regulation and functional activity of AS-NMD.
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DOI：
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发表时间：
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期刊：
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影响因子：
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DOI：
10.1523/jneurosci.1034-10.2011
发表时间：
2011-01-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
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通讯作者：
Roche KW
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