Regulation of Dscam exon 17 alternative splicing by steric hindrance in combination with RNA secondary structures
Regulation of Dscam exon 17 alternative splicing by steric hindrance in combination with RNA secondary structures
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通过空间位阻与 RNA 二级结构相结合调节 Dscam 外显子 17 选择性剪接
DOI：
10.4161/rna.27176
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发表时间：
2013-11
期刊：
影响因子：
4.1
通讯作者：
Yongfeng Jin
中科院分区：
文献类型：
--
作者：
Huawei Pan;Ran Chen;Feng Shi;Yongfeng Jin
唐氏综合征细胞粘附分子（Dscam）基因可能编码38 016个不同的异构体在果蝇通过互斥剪接。在这里，我们揭示了Dscam外显子17互斥剪接通过空间位阻与RNA二级结构相结合的调控组合机制。由于双翅目中外显子17.2分支点与外显子17.1非常接近，以及非双翅目物种中的间隔大小限制，这种相互排斥的行为受到空间位阻的影响。此外，内含子-外显子RNA结构在6个远亲目（双翅目、鳞翅目、鞘翅目、膜翅目、半翅目和Phthiraptera）的36个非果蝇物种中进化上保守，其通过掩蔽剪接位点来调节外显子17变体的选择。相比之下，以前未表征的RNA结构特异性激活外显子17.1，使剪接位点更紧密地在果蝇中，而其他适度抑制外显子17.1的选择，通过阻碍多聚嘧啶序列的访问。综上所述，这些数据表明，在跨越3亿多年的昆虫进化中，Dscam外显子17的调节选择性剪接的复杂性增加。这些结果还提供了通过空间位阻结合动态结构代码调节选择性剪接的模型。
The gene Down syndrome cell adhesion molecule (Dscam) potentially encodes 38 016 distinct isoforms in Drosophila melanogaster via mutually exclusive splicing. Here we reveal a combinatorial mechanism of regulation of Dscam exon 17 mutually exclusive splicing through steric hindrance in combination with RNA secondary structure. This mutually exclusive behavior is enforced by steric hindrance, due to the close proximity of the exon 17.2 branch point to exon 17.1 in Diptera, and the interval size constraint in non-Dipteran species. Moreover, intron-exon RNA structures are evolutionarily conserved in 36 non-Drosophila species of six distantly related orders (Diptera, Lepidoptera, Coleoptera, Hymenoptera, Hemiptera, and Phthiraptera), which regulates the selection of exon 17 variants via masking the splice site. By contrast, a previously uncharacterized RNA structure specifically activated exon 17.1 by bringing splice sites closer together in Drosophila, while the other moderately suppressed exon 17.1 selection by hindering the accessibility of polypyrimidine sequences. Taken together, these data suggest a phylogeny of increased complexity in regulating alternative splicing of Dscam exon 17 spanning more than 300 million years of insect evolution. These results also provide models of the regulation of alternative splicing through steric hindrance in combination with dynamic structural codes.
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影响因子：
64.8
作者：
通讯作者：
--
影响因子：
4.8
作者：
Muh, SJ;Hovhannisyan, RH;Carstens, RP
通讯作者：
Carstens, RP
影响因子：
64.5
作者：
Graveley, BR
通讯作者：
Graveley, BR
影响因子：
16.2
作者：
Zhan, XL;Clemens, JC;Zipursky, SL
通讯作者：
Zipursky, SL
可变窗口绑定，用于相互排斥的替代剪接。
影响因子：
12.3
作者：
Anastassiou, Dimitris;Liu, Hairuo;Varadan, Vinay
通讯作者：
Varadan, Vinay