A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons.
A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons.
复制标题
祖先剪接因子中的一个新蛋白质结构域驱动了神经微外显子的进化。
DOI：
10.1038/s41559-019-0813-6
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发表时间：
2019
影响因子：
16.8
通讯作者：
Torres-Méndez A
中科院分区：
文献类型：
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作者：
Torres-Méndez A
整个基因调控程序在进化过程中出现的机制还知之甚少。神经元微外显子是脊椎动物中最保守的选择性剪接类型，对大脑的正常发育和功能至关重要。在这里，我们发现了非脊椎动物物种中的神经微外显子程序，并通过出现以前未被描述的微外显子增强子(主)蛋白结构域将其起源追溯到双边祖先。主结构域起源于泛真核剪接因子基因的一种替代的、神经丰富的剪接异构体，随后固定在脊椎动物和神经元特异的剪接调节子Srrm4/nSR100及其类似的Srrm3中。值得注意的是，主位结构域是微外显子剪接的必要条件和充分条件，并通过与识别外显子所需的最早成分相互作用来发挥作用。神经系统中表达受限的新结构域的出现导致了剪接程序的进化，从而定性地扩大了双侧神经分子的复杂性。
The mechanisms by which entire programmes of gene regulation emerged during evolution are poorly understood. Neuronal microexons represent the most conserved class of alternative splicing in vertebrates, and are critical for proper brain development and function. Here, we discover neural microexon programmes in non-vertebrate species and trace their origin to bilaterian ancestors through the emergence of a previously uncharacterized ‘enhancer of microexons’ (eMIC) protein domain. The eMIC domain originated as an alternative, neural-enriched splice isoform of the pan-eukaryoticSrrm2/SRm300splicing factor gene, and subsequently became fixed in the vertebrate and neuronal-specific splicing regulatorSrrm4/nSR100and its paralogueSrrm3. Remarkably, the eMIC domain is necessary and sufficient for microexon splicing, and functions by interacting with the earliest components required for exon recognition. The emergence of a novel domain with restricted expression in the nervous system thus resulted in the evolution of splicing programmes that qualitatively expanded the neuronal molecular complexity in bilaterians.