A highly conserved program of neuronal microexons is misregulated in autistic brains.
A highly conserved program of neuronal microexons is misregulated in autistic brains.
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DOI：
10.1016/j.cell.2014.11.035
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发表时间：
2014-12-18
期刊：
影响因子：
64.5
通讯作者：
Blencowe BJ
中科院分区：
文献类型：
--
作者：
Irimia M;Weatheritt RJ;Ellis JD;Parikshak NN;Gonatopoulos-Pournatzis T;Babor M;Quesnel-Vallières M;Tapial J;Raj B;O'Hanlon D;Barrios-Rodiles M;Sternberg MJ;Cordes SP;Roth FP;Wrana JL;Geschwind DH;Blencowe BJ
选择性剪接（AS）产生巨大的转录组和蛋白质组的复杂性。然而，检测到的AS事件的无数提供重要的生物学功能还没有很好地理解。在这里，我们定义了迄今为止在哺乳动物中描述的功能协调、神经调节的AS的最大程序。相对于该程序中的所有其他类型的AS，3-15个核苷酸的“微外显子”显示出最显着的进化保守性和开关样调节。这些微外显子调节参与神经发生的蛋白质的相互作用结构域的功能。大多数神经微外显子由神经元特异性剪接因子nSR 100/SRRM 4通过其与相邻内含子增强子基序的结合来调节。神经微外显子在自闭症谱系障碍患者的大脑中经常失调，这种失调与nSR 100水平降低有关。因此，结果揭示了一个高度保守的程序，动态微外显子调控与重塑蛋白质相互作用网络在神经发生，其中的失调与自闭症。
Alternative splicing (AS) generates vast transcriptomic and proteomic complexity. However, which of the myriad of detected AS events provide important biological functions is not well understood. Here, we define the largest program of functionally coordinated, neural-regulated AS described to date in mammals. Relative to all other types of AS within this program, 3-15 nucleotide ‘microexons’ display the most striking evolutionary conservation and switch-like regulation. These microexons modulate the function of interaction domains of proteins involved in neurogenesis. Most neural microexons are regulated by the neuronal-specific splicing factor nSR100/SRRM4, through its binding to adjacent intronic enhancer motifs. Neural microexons are frequently misregulated in the brains of individuals with autism spectrum disorder, and this misregulation is associated with reduced levels of nSR100. The results thus reveal a highly conserved program of dynamic microexon regulation associated with the remodeling of protein interaction networks during neurogenesis, the misregulation of which is linked to autism.
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影响因子：
12.3
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影响因子：
64.8
作者：
BEACHY, PA;HELFAND, SL;HOGNESS, DS
通讯作者：
HOGNESS, DS
影响因子：
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作者：
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作者：
Braunschweig U;Barbosa-Morais NL;Pan Q;Nachman EN;Alipanahi B;Gonatopoulos-Pournatzis T;Frey B;Irimia M;Blencowe BJ
通讯作者：
Blencowe BJ
影响因子：
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作者：
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通讯作者：
Südhof, TC