Journal
NATURE
Volume 491, Issue 7423, Pages 284-U157Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature11509
Keywords
-
Categories
Funding
- Japan Society for the Promotion of Science (JSPS)
- Core Research for Evolutional Science and Technology (CREST) program 'The Creation of Basic Medical Technologies to Clarify and Control the Mechanisms Underlying Chronic Inflammation' of the Japan Science and Technology Agency (JST)
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan
- Grants-in-Aid for Scientific Research [20221008, 22687007, 10J56562, 23687014, 22117007, 11J05211] Funding Source: KAKEN
Ask authors/readers for more resources
PIWI-interacting RNAs (piRNAs) silence transposons to maintain genome integrity in animal germ lines(1-4). piRNAs are classified as primary and secondary piRNAs, depending on their biogenesis machinery(5-10). Primary piRNAs are processed from long non-coding RNA precursors transcribed from piRNA clusters in the genome through the primary processing pathway(5,8-10). Although the existence of a ribonuclease participating in this pathway has been predicted, its molecular identity remained unknown. Here we show that Zucchini (Zuc), a mitochondrial phospholipase D (PLD) superfamily member(11), is an endoribonuclease essential for primary piRNA biogenesis. We solved the crystal structure of Drosophila melanogaster Zuc (DmZuc) at 1.75 angstrom resolution. The structure revealed that DmZuc has a positively charged, narrow catalytic groove at the dimer interface, which could accommodate a single-stranded, but not a double-stranded, RNA. DmZuc and the mouse homologue MmZuc (also known as Pld6 and MitoPLD)(12-14) showed endoribonuclease activity for single-stranded RNAs in vitro. The RNA cleavage products bear a 5'-monophosphate group, a hallmark of mature piRNAs. Mutational analyses revealed that the conserved active-site residues of DmZuc are critical for the ribonuclease activity in vitro, and for piRNA maturation and transposon silencing in vivo. We propose a model for piRNA biogenesis in animal germ lines, in which the Zuc endoribonuclease has a key role in primary piRNA maturation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available