Crystal structure and activity of the endoribonuclease domain of the piRNA pathway factor maelstrom

Naoki Matsumoto, Kaoru Sato, Hiroshi Nishimasu, Yurika Namba, Kana Miyakubi, Naoshi Dohmae, Ryuichiro Ishitani, Haruhiko Siomi, Mikiko C. Siomi, Osamu Nureki

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 1.6Å 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.

Original languageEnglish
Pages (from-to)366-375
Number of pages10
JournalCell Reports
Volume11
Issue number3
DOIs
Publication statusPublished - 2015 Apr 21

Fingerprint

Endoribonucleases
Small Interfering RNA
Ribonuclease H
Crystal structure
RNA
Drosophila
RNA Cleavage
Endonucleases
Gonads
Drosophila melanogaster
Animals
Genes
Genome
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Matsumoto, N., Sato, K., Nishimasu, H., Namba, Y., Miyakubi, K., Dohmae, N., ... Nureki, O. (2015). Crystal structure and activity of the endoribonuclease domain of the piRNA pathway factor maelstrom. Cell Reports, 11(3), 366-375. https://doi.org/10.1016/j.celrep.2015.03.030

Crystal structure and activity of the endoribonuclease domain of the piRNA pathway factor maelstrom. / Matsumoto, Naoki; Sato, Kaoru; Nishimasu, Hiroshi; Namba, Yurika; Miyakubi, Kana; Dohmae, Naoshi; Ishitani, Ryuichiro; Siomi, Haruhiko; Siomi, Mikiko C.; Nureki, Osamu.

In: Cell Reports, Vol. 11, No. 3, 21.04.2015, p. 366-375.

Research output: Contribution to journalArticle

Matsumoto, N, Sato, K, Nishimasu, H, Namba, Y, Miyakubi, K, Dohmae, N, Ishitani, R, Siomi, H, Siomi, MC & Nureki, O 2015, 'Crystal structure and activity of the endoribonuclease domain of the piRNA pathway factor maelstrom', Cell Reports, vol. 11, no. 3, pp. 366-375. https://doi.org/10.1016/j.celrep.2015.03.030
Matsumoto, Naoki ; Sato, Kaoru ; Nishimasu, Hiroshi ; Namba, Yurika ; Miyakubi, Kana ; Dohmae, Naoshi ; Ishitani, Ryuichiro ; Siomi, Haruhiko ; Siomi, Mikiko C. ; Nureki, Osamu. / Crystal structure and activity of the endoribonuclease domain of the piRNA pathway factor maelstrom. In: Cell Reports. 2015 ; Vol. 11, No. 3. pp. 366-375.
@article{ded04b2b69e341bba775c551585aae24,
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{\AA} 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.",
author = "Naoki Matsumoto and Kaoru Sato and Hiroshi Nishimasu and Yurika Namba and Kana Miyakubi and Naoshi Dohmae and Ryuichiro Ishitani and Haruhiko Siomi and Siomi, {Mikiko C.} and Osamu Nureki",
year = "2015",
month = "4",
day = "21",
doi = "10.1016/j.celrep.2015.03.030",
language = "English",
volume = "11",
pages = "366--375",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Crystal structure and activity of the endoribonuclease domain of the piRNA pathway factor maelstrom

AU - Matsumoto, Naoki

AU - Sato, Kaoru

AU - Nishimasu, Hiroshi

AU - Namba, Yurika

AU - Miyakubi, Kana

AU - Dohmae, Naoshi

AU - Ishitani, Ryuichiro

AU - Siomi, Haruhiko

AU - Siomi, Mikiko C.

AU - Nureki, Osamu

PY - 2015/4/21

Y1 - 2015/4/21

N2 - 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 1.6Å 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.

AB - 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 1.6Å 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.

UR - http://www.scopus.com/inward/record.url?scp=84928210333&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928210333&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2015.03.030

DO - 10.1016/j.celrep.2015.03.030

M3 - Article

C2 - 25865890

AN - SCOPUS:84928210333

VL - 11

SP - 366

EP - 375

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 3

ER -