Molecular basis for PICS-mediated piRNA biogenesis and cell division

Xiaoyang Wang, Chenming Zeng, Shanhui Liao, Zhongliang Zhu, Jiahai Zhang, Xiaoming Tu, Xuebiao Yao, Xuezhu Feng (), Shouhong Guang () and Chao Xu ()
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Xiaoyang Wang: University of Science and Technology of China
Chenming Zeng: University of Science and Technology of China
Shanhui Liao: University of Science and Technology of China
Zhongliang Zhu: University of Science and Technology of China
Jiahai Zhang: University of Science and Technology of China
Xiaoming Tu: University of Science and Technology of China
Xuebiao Yao: University of Science and Technology of China
Xuezhu Feng: University of Science and Technology of China
Shouhong Guang: University of Science and Technology of China
Chao Xu: University of Science and Technology of China

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract By incorporating two mutually exclusive factors, PID-1 and TOST-1, C. elegans PICS complex plays important roles in piRNA biogenesis, chromosome segregation and cell division. We firstly map the interaction network between PICS subunits, then uncover the mechanisms underlying the interactions between PICS subunits by solving several complex structures, including those of TOFU-6/PICS-1, ERH-2/PICS-1, and ERH-2/TOST-1. Our biochemical experiment also demonstrates that PICS exists as an octamer consisting of two copies of each subunit. Combining structural analyses with mutagenesis experiments, we identify interfacial residues of PICS subunits that are critical for maintaining intact PICS complex in vitro. Furthermore, using genetics, cell biology and imaging experiments, we find that those mutants impairing the in vitro interaction network within PICS, also lead to dysfunction of PICS in vivo, including mislocalization of PICS, and reduced levels of piRNAs or aberrant chromosome segregation and cell division. Therefore, our work provides structural insights into understanding the PICS-mediated piRNA biogenesis and cell division.

Date: 2021
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DOI: 10.1038/s41467-021-25896-7

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