Structural analysis of Dis3l2, an exosome-independent exonuclease from Schizosaccharomyces pombe
Structural analysis of Dis3l2, an exosome-independent exonuclease from Schizosaccharomyces pombe
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Dis3l2（一种来自粟酒裂殖酵母的外泌体独立核酸外切酶）的结构分析。
DOI：
10.1107/s1399004715005805
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发表时间：
2015-06-01
影响因子：
2.2
通讯作者：
Li, Xu
中科院分区：
文献类型：
--
作者：
Lv, Hui;Zhu, Yuwei;Li, Xu
在去腺苷化和去帽后，细胞质mRNA可以在两个相反的方向上被消化：在5 '-3'方向上被Xrn 1消化或在3 '-5'方向上被外泌体复合物消化。最近，已经描述了一种涉及Dis 3l 2的新的3 '-5' RNA衰变途径，其不同于Xrn 1和外泌体的降解。粟酒裂殖酵母基因SPAC2C4.07c的产物被鉴定为人Dis 312的同源物。在这项工作中，2.8埃分辨率的X射线晶体结构的S。本文报道了粟酒裂殖酵母Dis 3l 2（SpDis 3l 2），它的构象与同源小鼠Dis 3l 2-RNA复合物中的构象明显不同。荧光偏振实验表明，RNB和S1是SpDis 312的主要RNA结合结构域，而CSD（CSD 1和CSD 2）在SpDis 312的RNA结合过程中起着不可或缺的作用。将结构比较和致突变实验结合在一起，可以推断SpDis 3l 2的RNA识别模式类似于其小鼠同源物，而不是大肠杆菌RNase II-RNA复合物。此外，在RNA底物与SpDis 312结合后可能发生剧烈的构象变化。
After deadenylation and decapping, cytoplasmic mRNA can be digested in two opposite directions: in the 5'-3' direction by Xrn1 or in the 3'-5' direction by the exosome complex. Recently, a novel 3'-5' RNA-decay pathway involving Dis3l2 has been described that differs from degradation by Xrn1 and the exosome. The product of the Schizosaccharomyces pombe gene SPAC2C4.07c was identified as a homologue of human Dis3l2. In this work, the 2.8 angstrom resolution X-ray crystal structure of S. pombe Dis3l2 (SpDis3l2) is reported, the conformation of which is obviously different from that in the homologous mouse Dis3l2-RNA complex. Fluorescence polarization assay experiments showed that RNB and S1 are the primary RNA-binding domains and that the CSDs (CSD1 and CSD2) play an indispensable role in the RNA-binding process of SpDis3l2. Taking the structure comparison and mutagenic experiments together, it can be inferred that the RNA-recognition pattern of SpDis3l2 resembles that of its mouse homologue rather than that of the Escherichia coli RNase II-RNA complex. Furthermore, a drastic conformation change could occur following the binding of the RNA substrate to SpDis3l2.