一种保守的PIWI沉默复合体可检测piRNA与靶标的结合。
A conserved PIWI silencing complex detects piRNA-target engagement.
作者信息
De Dipayan, Sarkar Sucharita, Gebert Luca F R, Wiryaman Timothy, Anzelon Todd A, MacRae Ian J
机构信息
Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.
Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.
出版信息
Mol Cell. 2025 Sep 4;85(17):3275-3287.e7. doi: 10.1016/j.molcel.2025.08.010.
In animal germ cells, PIWI proteins use piRNAs to detect active selfish genetic elements. Base-pairing to a piRNA defines transposon recognition, but how this interaction triggers a defensive response remains unclear. Here, we identify a transposon recognition complex composed of the silkworm proteins Siwi, GTSF1, and Maelstrom. Biochemical and cryo-electron microscopy (cryo-EM) analyses show that extended piRNA-target pairing locks Siwi in a conformation that recruits GTSF1 and Maelstrom. Extended piRNA-target pairing is recognized by the N-terminal helix of Maelstrom and the first zinc finger of GTSF1, which act together to hold Siwi in an endonucleolytically active state. The resulting activated complex, termed Siwi, rapidly cleaves target RNAs and recruits the piRNA biogenesis factor Spindle-E. Structural predictions reveal related complexes in animals ranging from humans to sponges, indicating PIWI assembly is a conserved transposon recognition mechanism employed broadly across the metazoan kingdom.
在动物生殖细胞中，PIWI蛋白利用piRNA来检测活跃的自私遗传元件。与piRNA的碱基配对决定了转座子的识别，但这种相互作用如何触发防御反应仍不清楚。在这里，我们鉴定出一种由家蚕蛋白Siwi、GTSF1和Maelstrom组成的转座子识别复合体。生化分析和冷冻电子显微镜（cryo-EM）分析表明，延长的piRNA-靶标配对将Siwi锁定在一种构象中，这种构象会招募GTSF1和Maelstrom。延长的piRNA-靶标配对被Maelstrom的N端螺旋和GTSF1的第一个锌指识别，它们共同作用使Siwi保持在内切核酸酶活性状态。由此产生的活化复合体，称为Siwi，能迅速切割靶RNA并招募piRNA生物合成因子Spindle-E。结构预测揭示了从人类到海绵动物等动物中的相关复合体，表明PIWI组装是一种广泛应用于后生动物界的保守转座子识别机制。
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