Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals.
Parallel evolution of a splicing program controlling neuronal excitability in flies and mammals.
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DOI：
10.1126/sciadv.abk0445
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发表时间：
2022-01-28
期刊：
影响因子：
13.6
通讯作者：
Irimia M
中科院分区：
文献类型：
--
作者：
Torres-Méndez A;Pop S;Bonnal S;Almudi I;Avola A;Roberts RJV;Paolantoni C;Alcaina-Caro A;Martín-Anduaga A;Haussmann IU;Morin V;Casares F;Soller M;Kadener S;Roignant JY;Prieto-Godino L;Irimia M
选择性剪接增加了整个动物胚胎发育过程中神经元转录组的复杂性。为了深入研究控制这一调控层的组装和进化的机制，我们描述了果蝇神经元微外显子程序的特征，并将其与哺乳动物进行了比较。在非脊椎动物bilaterians，这种剪接程序被限制在神经元的转录后加工的增强子的微外显子（eMIC）结构域Srrm 234。在果蝇中，这种处理依赖于Elav/Fne的调节。eMIC缺陷或错误表达导致广泛的神经学改变，主要是由受损的神经元活性引起的，如神经元成像实验和细胞类型特异性拯救的组合所揭示的。这些缺陷与短神经外显子的全基因组跳跃相关，这些外显子在离子通道中强烈富集。我们没有发现果蝇和小鼠之间的eMIC调控的外显子重叠，说明了古老的转录后程序如何在不同的门中独立进化，以影响不同的细胞模块，同时保持细胞类型的特异性。果蝇和哺乳动物中的神经元微外显子影响不同的细胞模块，同时共享调节和细胞类型特异性。
Alternative splicing increases neuronal transcriptomic complexity throughout animal phylogeny. To delve into the mechanisms controlling the assembly and evolution of this regulatory layer, we characterized the neuronal microexon program in Drosophila and compared it with that of mammals. In nonvertebrate bilaterians, this splicing program is restricted to neurons by the posttranscriptional processing of the enhancer of microexons (eMIC) domain in Srrm234. In Drosophila, this processing is dependent on regulation by Elav/Fne. eMIC deficiency or misexpression leads to widespread neurological alterations largely emerging from impaired neuronal activity, as revealed by a combination of neuronal imaging experiments and cell type–specific rescues. These defects are associated with the genome-wide skipping of short neural exons, which are strongly enriched in ion channels. We found no overlap of eMIC-regulated exons between flies and mice, illustrating how ancient posttranscriptional programs can evolve independently in different phyla to affect distinct cellular modules while maintaining cell-type specificity. Neuronal microexons in flies and mammals affect disparate cellular modules while sharing regulatory and cell-type specificity.
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影响因子：
64.8
作者：
通讯作者：
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影响因子：
16
作者：
Gonatopoulos-Pournatzis, Thomas;Wu, Mingkun;Blencowe, Benjamin J.
通讯作者：
Blencowe, Benjamin J.
影响因子：
7
作者：
Brooks, Angela N.;Yang, Li;Graveley, Brenton R.
通讯作者：
Graveley, Brenton R.
影响因子：
64.8
作者：
Graveley BR;Brooks AN;Carlson JW;Duff MO;Landolin JM;Yang L;Artieri CG;van Baren MJ;Boley N;Booth BW;Brown JB;Cherbas L;Davis CA;Dobin A;Li R;Lin W;Malone JH;Mattiuzzo NR;Miller D;Sturgill D;Tuch BB;Zaleski C;Zhang D;Blanchette M;Dudoit S;Eads B;Green RE;Hammonds A;Jiang L;Kapranov P;Langton L;Perrimon N;Sandler JE;Wan KH;Willingham A;Zhang Y;Zou Y;Andrews J;Bickel PJ;Brenner SE;Brent MR;Cherbas P;Gingeras TR;Hoskins RA;Kaufman TC;Oliver B;Celniker SE
通讯作者：
Celniker SE
影响因子：
14.9
作者：
Henry GL;Davis FP;Picard S;Eddy SR
通讯作者：
Eddy SR