C. elegans orthologs MUT-7/CeWRN-1 of Werner syndrome protein regulate neuronal plasticity.
C. elegans orthologs MUT-7/CeWRN-1 of Werner syndrome protein regulate neuronal plasticity.
复制标题
线虫同源Werner综合征蛋白mut7 /CeWRN-1调控神经元可塑性。
DOI：
10.7554/elife.62449
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发表时间：
2021-03-01
期刊：
影响因子：
7.7
通讯作者：
Juang BT
中科院分区：
文献类型：
--
作者：
Hsu TY;Zhang B;L'Etoile ND;Juang BT
秀丽隐杆线虫将人类Werner综合征蛋白（WRN）同源物表达为两种不同的蛋白：具有3 ‘−5 ’外切酶结构域的mut7和具有解旋酶结构域的CeWRN-1。这些领域如何合作仍不清楚。在这里，我们展示了MUT-7和CeWRN-1对22G小干扰RNA （siRNA）合成和神经元信号传导的可塑性的不同贡献。mut7在细胞质中特异地促进siRNA的生物发生，并在细胞核中与CeWRN-1结合。核Argonaute NRDE-3输入siRNA促进异染色质结合蛋白HP1同源物HPL-2装载到特定位点。这种异染色质复合物抑制关酰环化酶ODR-1的基因表达，从而指导秀丽隐杆线虫的嗅觉可塑性。我们的研究结果表明，人类WRN的外切酶和解旋酶结构域可能协同作用，促进rna依赖的负载进入异染色质复合体，这整个过程的失败降低了有丝分裂后神经元的可塑性。
Caenorhabditis elegans expresses human Werner syndrome protein (WRN) orthologs as two distinct proteins: MUT-7, with a 3′−5′ exonuclease domain, and CeWRN-1, with helicase domains. How these domains cooperate remains unclear. Here, we demonstrate the different contributions of MUT-7 and CeWRN-1 to 22G small interfering RNA (siRNA) synthesis and the plasticity of neuronal signaling. MUT-7 acts specifically in the cytoplasm to promote siRNA biogenesis and in the nucleus to associate with CeWRN-1. The import of siRNA by the nuclear Argonaute NRDE-3 promotes the loading of the heterochromatin-binding protein HP1 homolog HPL-2 onto specific loci. This heterochromatin complex represses the gene expression of the guanylyl cyclase ODR-1 to direct olfactory plasticity in C. elegans. Our findings suggest that the exonuclease and helicase domains of human WRN may act in concert to promote RNA-dependent loading into a heterochromatin complex, and the failure of this entire process reduces plasticity in postmitotic neurons.