Metazoan Maelstrom is an RNA-binding protein that has evolved from an ancient nuclease active in protists

RNA. 2015 May;21(5):833-9. doi: 10.1261/rna.049437.114. Epub 2015 Mar 16.


Piwi-interacting RNAs (piRNAs) guide Piwi argonautes to their transposon targets for silencing. The highly conserved protein Maelstrom is linked to both piRNA biogenesis and effector roles in this pathway. One defining feature of Maelstrom is the predicted MAEL domain of unknown molecular function. Here, we present the first crystal structure of the MAEL domain from Bombyx Maelstrom, which reveals a nuclease fold. The overall architecture resembles that found in Mg(2+)- or Mn(2+)-dependent DEDD nucleases, but a clear distinguishing feature is the presence of a structural Zn(2+) ion coordinated by the conserved ECHC residues. Strikingly, metazoan Maelstrom orthologs across the animal kingdom lack the catalytic DEDD residues, and as we show for Bombyx Maelstrom are inactive as nucleases. However, a MAEL domain-containing protein from amoeba having both sequence motifs (DEDD and ECHC) is robustly active as an exoribonuclease. Finally, we show that the MAEL domain of Bombyx Maelstrom displays a strong affinity for single-stranded RNAs. Our studies suggest that the ancient MAEL nuclease domain evolved to function as an RNA-binding module in metazoan Maelstrom.

Keywords: Bombyx; E. histolytica; EHI_192630; MAEL; Piwi; piRNA; ribonuclease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bombyx / genetics
  • Bombyx / metabolism*
  • Crystallography, X-Ray
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Evolution, Molecular*
  • Insect Proteins / chemistry*
  • Insect Proteins / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • RNA, Small Interfering / metabolism*
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • Ribonucleases / chemistry*
  • Ribonucleases / genetics
  • Sequence Homology


  • Drosophila Proteins
  • Insect Proteins
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • mael protein, Drosophila
  • Ribonucleases