title: Crystal Structure and Activity of the Endoribonuclease Domain of the piRNA Pathway Factor Maelstrom.
abstract: PIWI-interacting RNAs (piRNAs) protect the genome from transposons in animal gonads. Maelstrom (Mael) is an evolutionarily conserved protein, composed of a high-mobility group (HMG) domain and a MAEL domain, and is essential for piRNA-mediated transcriptional transposon silencing in various species, such as Drosophila and mice. However, its structure and biochemical function have remained elusive. Here, we report the crystal structure of the MAEL domain from Drosophila melanogaster Mael, at 1.6 Å resolution. The structure reveals that the MAEL domain has an RNase H-like fold but lacks canonical catalytic residues conserved among RNase H-like superfamily nucleases. Our biochemical analyses reveal that the MAEL domain exhibits single-stranded RNA (ssRNA)-specific endonuclease activity. Our cell-based analyses further indicate that ssRNA cleavage activity appears dispensable for piRNA-mediated transcriptional transposon silencing in Drosophila. Our findings provide clues toward understanding the multiple roles of Mael in the piRNA pathway.
authors: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan.
authors: Naoki
authors: N
authors: Matsumoto
authors: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan.
authors: Kaoru
authors: K
authors: Sato
authors: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan; JST, PRESTO, Tokyo 113-0032, Japan.
authors: Hiroshi
authors: H
authors: Nishimasu
authors: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan.
authors: Yurika
authors: Y
authors: Namba
authors: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan.
authors: Kana
authors: K
authors: Miyakubi
authors: Biomolecular Characterization Team and CREST/JST, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors: Naoshi
authors: N
authors: Dohmae
authors: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan.
authors: Ryuichiro
authors: R
authors: Ishitani
authors: Department of Molecular Biology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors: Haruhiko
authors: H
authors: Siomi
authors: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan. Electronic address: siomim@bs.s.u-tokyo.ac.jp.
authors: Mikiko C
authors: MC
authors: Siomi
authors: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan. Electronic address: nureki@bs.s.u-tokyo.ac.jp.
authors: Osamu
authors: O
authors: Nureki
mesh_terms: D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism; D004722:Endoribonucleases / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D029721:Drosophila Proteins; D034741:RNA, Small Interfering; C109767:mael protein, Drosophila; D004722:Endoribonucleases