Phosphorylation regulates the activity of the SMN complex during assembly of spliceosomal U snRNPs
Phosphorylation regulates the activity of the SMN complex during assembly of spliceosomal U snRNPs
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DOI：
10.1038/sj.embor.7400301
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发表时间：
2005-01-01
期刊：
影响因子：
7.7
通讯作者：
Fischer, U
中科院分区：
文献类型：
--
作者：
Grimmler, M;Bauer, L;Fischer, U
剪接体富U小核核糖核蛋白（U snRNPs）的组装是由SMN和PRMT5复合物协同作用介导的atp依赖性过程。在这里，我们提供的证据表明，这种组装机制的活动是通过翻译后修饰的手段进行调节的。我们发现SMN/PRMT5系统的两个主要组成部分，即存活运动神经元（SMN）蛋白（其水平降低导致脊髓性肌萎缩）和pICln，在体内被磷酸化。这两种蛋白质都有一个先前未知的基序，包含一个或两个磷酸丝氨酸。SMN中这些残基（丝氨酸28和31）的改变会显著损害SMN复合物的活性。尽管SMN在细胞核和细胞质中都存在，但我们发现只有细胞质能促进SMN介导的U snRNP组装活性。由于细胞质中SMN的磷酸化程度要大得多，我们假设这种修饰是SMN复合物的关键激活因子。
The assembly of spliceosomal U-rich small nuclear ribonucleoproteins (U snRNPs) is an ATP-dependent process mediated by the coordinated action of the SMN and the PRMT5 complex. Here, we provide evidence that the activity of this assembly machinery is regulated by means of post-translational modification. We show that two main components of the SMN/PRMT5 system, namely the survival motor neuron (SMN) protein (reduced levels thereof causing spinal muscular atrophy) and pICln, are phosphorylated in vivo. Both proteins share a previously unknown motif containing either one or two phosphoserines. Alteration of these residues in SMN (serines 28 and 31) significantly impairs the activity of the SMN complex. Despite the presence of SMN in both the nucleus and cytoplasm, we find that only the latter promotes efficient SMN-mediated U snRNP assembly activity. As cytoplasmic SMN is phosphorylated to a much larger extent, we hypothesize that this modification is a key activator of the SMN complex.