Molecular basis for PICS-mediated piRNA biogenesis and cell division

Nat Commun. 2021 Sep 22;12(1):5595. doi: 10.1038/s41467-021-25896-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / chemistry*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Division*
  • Chromosome Segregation
  • Crystallography, X-Ray
  • Intracellular Space / metabolism
  • Multiprotein Complexes
  • Mutagenesis
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Protein Subunits
  • RNA, Small Interfering / biosynthesis*


  • Caenorhabditis elegans Proteins
  • Multiprotein Complexes
  • Protein Subunits
  • RNA, Small Interfering