A direct interaction between DCP1 and XRN1 couples mRNA decapping to 5′ exonucleolytic degradation
A direct interaction between DCP1 and XRN1 couples mRNA decapping to 5′ exonucleolytic degradation
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DOI：
10.1038/nsmb.2413
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发表时间：
2012-12-01
影响因子：
16.8
通讯作者：
Izaurralde, Elisa
中科院分区：
文献类型：
--
作者：
Braun, Joerg E.;Truffault, Vincent;Izaurralde, Elisa
去帽酶DCP2去除mRNA 5'帽结构会导致XRN1对mRNA进行快速的5'→3'降解，这表明这两个过程是相互协调的，但偶联机制尚不清楚。DCP2与去帽激活因子EDC4和DCP1相关联。在此我们表明，XRN1分别在人类和黑腹果蝇细胞中与EDC4和DCP1直接相互作用。在黑腹果蝇细胞中，这种相互作用是由DCP1的EVH1结构域和XRN1 C末端区域的一个DCP1结合基序（DBM）介导的。与DBM结合的DCP1 EVH1结构域的核磁共振结构显示，该肽段停靠在一个保守的芳香族裂隙处，EVH1结构域利用此裂隙识别富含脯氨酸的配体。我们的研究结果揭示了XRN1在去帽过程中的作用，并为去帽与5'→3'mRNA降解的偶联提供了分子基础。
The removal of the mRNA 5' cap structure by the decapping enzyme DCP2 leads to rapid 5'-> 3' mRNA degradation by XRN1, suggesting that the two processes are coordinated, but the coupling mechanism is unknown. DCP2 associates with the decapping activators EDC4 and DCP1. Here we show that XRN1 directly interacts with EDC4 and DCP1 in human and Drosophila melanogaster cells, respectively. In D. melanogaster cells, this interaction is mediated by the DCP1 EVH1 domain and a DCP1-binding motif (DBM) in the XRN1 C-terminal region. The NMR structure of the DCP1 EVH1 domain bound to the DBM reveals that the peptide docks at a conserved aromatic cleft, which is used by EVH1 domains to recognize proline-rich ligands. Our findings reveal a role for XRN1 in decapping and provide a molecular basis for the coupling of decapping to 5'-> 3' mRNA degradation.