Functional coordination of alternative splicing in the mammalian central nervous system.
Functional coordination of alternative splicing in the mammalian central nervous system.
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DOI：
10.1186/gb-2007-8-6-r108
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发表时间：
2007
期刊：
影响因子：
12.3
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中科院分区：
文献类型：
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微阵列分析提供了新的证据，表明哺乳动物中枢神经系统中特定的细胞过程在选择性剪接水平上是协调的，并且复杂的剪接密码是中枢神经系统特异性选择性剪接调控的基础。选择性剪接(AS)具有扩大蛋白质组复杂性的功能，在基因调控中扮演着许多重要的角色。然而，AS以细胞和组织类型特定的方式发挥作用的程度尚不清楚。此外，作为AS细胞和组织类型特异性调控基础的序列编码还知之甚少。使用定量AS微阵列图谱，我们已经确定了大量广泛表达的小鼠基因，这些基因包含单个或协调的可选外显子对，这些外显子以组织调控的方式剪接。其中大多数AS事件在中枢神经系统(CNS)组织中表现出不同的调控。大约一半的相应基因具有神经特异性功能，并在共同的过程和相互连接的途径中发挥作用。AS在中枢神经系统组织中的差异调控与一组主要位于内含子和构成外显子序列中的新基序密切相关，这些外显子序列与中枢神经系统调节的替代外显子相邻。这些基序的不同亚集与CNS组织中相对于其他轮廓组织的更多的包含性或更多的替代外显子的排除相关。我们的发现提供了新的证据，表明哺乳动物CNS中的特定细胞过程在AS水平上是协调的，并且复杂的剪接密码是CNS特异性AS调控的基础。该密码似乎包含许多新的基序，其中一些位于与受调控的替代外显子相邻的结构性外显子中。这些数据为理解广泛表达的基因的组织特异性功能在AS水平上协调的分子机制提供了基础。
A microarray analysis provides new evidence suggesting that specific cellular processes in the mammalian CNS are coordinated at the level of alternative splicing, and that a complex splicing code underlies CNS-specific alternative splicing regulation. Alternative splicing (AS) functions to expand proteomic complexity and plays numerous important roles in gene regulation. However, the extent to which AS coordinates functions in a cell and tissue type specific manner is not known. Moreover, the sequence code that underlies cell and tissue type specific regulation of AS is poorly understood. Using quantitative AS microarray profiling, we have identified a large number of widely expressed mouse genes that contain single or coordinated pairs of alternative exons that are spliced in a tissue regulated fashion. The majority of these AS events display differential regulation in central nervous system (CNS) tissues. Approximately half of the corresponding genes have neural specific functions and operate in common processes and interconnected pathways. Differential regulation of AS in the CNS tissues correlates strongly with a set of mostly new motifs that are predominantly located in the intron and constitutive exon sequences neighboring CNS-regulated alternative exons. Different subsets of these motifs are correlated with either increased inclusion or increased exclusion of alternative exons in CNS tissues, relative to the other profiled tissues. Our findings provide new evidence that specific cellular processes in the mammalian CNS are coordinated at the level of AS, and that a complex splicing code underlies CNS specific AS regulation. This code appears to comprise many new motifs, some of which are located in the constitutive exons neighboring regulated alternative exons. These data provide a basis for understanding the molecular mechanisms by which the tissue specific functions of widely expressed genes are coordinated at the level of AS.