Sumoylation regulates the assembly and activity of the SMN complex.
Sumoylation regulates the assembly and activity of the SMN complex.
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SUMO化调节SMN复合物的组装和活性。
DOI：
10.1038/s41467-021-25272-5
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发表时间：
2021-08-19
影响因子：
16.6
通讯作者：
Lotti F
中科院分区：
文献类型：
--
作者：
Riboldi GM;Faravelli I;Kuwajima T;Delestrée N;Dermentzaki G;De Planell-Saguer M;Rinchetti P;Hao LT;Beattie CC;Corti S;Przedborski S;Mentis GZ;Lotti F
SMN是一种普遍表达的蛋白质，对生命至关重要。SMN缺乏导致神经退行性疾病脊髓性肌萎缩症（SMA），这是婴儿死亡的主要遗传原因。SMN与自身和其他蛋白质相互作用，形成复合物，在核糖核蛋白的组装中发挥作用。SMN被SUMO（小泛素样修饰物）修饰，但尚不清楚SMN与SMA发病机制相关的功能是否需要SUMO化。在这里，我们表明，一个SUMO相互作用的基序（SIM）的失活改变SMN亚细胞分布，其复杂的完整性，其功能的小核核糖核蛋白的生物合成。在SMA小鼠模型中表达SMN的SIM失活突变体略微延长了存活率，并对运动缺陷进行了有限和短暂的纠正。值得注意的是，尽管SIM失活的SMN减弱运动神经元的损失并改善神经肌肉接头突触，但它未能防止感觉-运动突触的损失。这些研究结果表明，SUMO化是重要的SMN复合物的正确组装和功能，这种翻译后修饰的损失损害的能力，SMN纠正SMA小鼠的感觉运动回路中的选择性缺陷。SUMO化对于SMN复合物的组装和功能是重要的，SMN复合物在RNA加工中起核心作用。在这里，作者表明，这种翻译后修饰的损失损害了SMN的能力，以纠正脊髓性肌萎缩症的动物模型的感觉运动回路的选择性缺陷。
SMN is a ubiquitously expressed protein and is essential for life. SMN deficiency causes the neurodegenerative disease spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. SMN interacts with itself and other proteins to form a complex that functions in the assembly of ribonucleoproteins. SMN is modified by SUMO (Small Ubiquitin-like Modifier), but whether sumoylation is required for the functions of SMN that are relevant to SMA pathogenesis is not known. Here, we show that inactivation of a SUMO-interacting motif (SIM) alters SMN sub-cellular distribution, the integrity of its complex, and its function in small nuclear ribonucleoproteins biogenesis. Expression of a SIM-inactivated mutant of SMN in a mouse model of SMA slightly extends survival rate with limited and transient correction of motor deficits. Remarkably, although SIM-inactivated SMN attenuates motor neuron loss and improves neuromuscular junction synapses, it fails to prevent the loss of sensory-motor synapses. These findings suggest that sumoylation is important for proper assembly and function of the SMN complex and that loss of this post-translational modification impairs the ability of SMN to correct selective deficits in the sensory-motor circuit of SMA mice. Sumoylation is important for the assembly and function of the SMN complex, which plays a central role in RNA processing. Here the authors show that loss of this posttranslational modification impairs the ability of SMN to correct selective deficits in the sensory-motor circuit of animal models of spinal muscular atrophy.
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影响因子：
11.2
作者：
Duque, Sandra I.;Arnold, W. David;Odermatt, Philipp;Li, Xiaohui;Porensky, Paul N.;Schmelzer, Leah;Meyer, Kathrin;Kolb, Stephen J.;Schuemperli, Daniel;Kaspar, Brian K.;Burghes, Arthur H. M.
通讯作者：
Burghes, Arthur H. M.
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
5.8
作者：
Beauclair, Guillaume;Bridier-Nahmias, Antoine;Zamborlini, Alessia
通讯作者：
Zamborlini, Alessia
影响因子：
4.5
作者：
Bäumer D;Lee S;Nicholson G;Davies JL;Parkinson NJ;Murray LM;Gillingwater TH;Ansorge O;Davies KE;Talbot K
通讯作者：
Talbot K
影响因子：
15.1
作者：
Hao le T;Burghes AH;Beattie CE
通讯作者：
Beattie CE