title: The RNA helicase MOV10L1 binds piRNA precursors to initiate piRNA processing.
abstract: Piwi-piRNA (Piwi-interacting RNA) ribonucleoproteins (piRNPs) enforce retrotransposon silencing, a function critical for preserving the genome integrity of germ cells. The molecular functions of most of the factors that have been genetically implicated in primary piRNA biogenesis are still elusive. Here we show that MOV10L1 exhibits 5'-to-3' directional RNA-unwinding activity in vitro and that a point mutation that abolishes this activity causes a failure in primary piRNA biogenesis in vivo. We demonstrate that MOV10L1 selectively binds piRNA precursor transcripts and is essential for the generation of intermediate piRNA processing fragments that are subsequently loaded to Piwi proteins. Multiple analyses suggest an intimate coupling of piRNA precursor processing with elements of local secondary structures such as G quadruplexes. Our results support a model in which MOV10L1 RNA helicase activity promotes unwinding and funneling of the single-stranded piRNA precursor transcripts to the endonuclease that catalyzes the first cleavage step of piRNA processing.
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Neuropathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Anastassios
authors.initials: A
authors.lastname: Vourekas
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China; mourelaz@uphs.upenn.edu kezheng@njmu.edu.cn pwang@vet.upenn.edu.
authors.forename: Ke
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Qi
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Neuropathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Manolis
authors.initials: M
authors.lastname: Maragkakis
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Neuropathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Alexiou
authors.affiliation: State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China;
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: European Molecular Biology Laboratory, Grenoble Outstation, 38042 Grenoble, Cedex 9, France.
authors.forename: Ramesh S
authors.initials: RS
authors.lastname: Pillai
authors.affiliation: Department of Pathology and Laboratory Medicine, Division of Neuropathology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; mourelaz@uphs.upenn.edu kezheng@njmu.edu.cn pwang@vet.upenn.edu.
authors.forename: Zissimos
authors.initials: Z
authors.lastname: Mourelatos
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; mourelaz@uphs.upenn.edu kezheng@njmu.edu.cn pwang@vet.upenn.edu.
authors.forename: P Jeremy
authors.initials: PJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D005260:Female; D054856:G-Quadruplexes; D008297:Male; D051379:Mice; D011485:Protein Binding; D017433:Protein Structure, Secondary; D020365:RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism
chemical_list: D012322:RNA Precursors; D034741:RNA, Small Interfering; D012261:Ribonucleoproteins; C477006:Mov10l1 protein, mouse; D020365:RNA Helicases
keywords: Argonaute; Armitage; G quadruplex; MOV10L1; Piwi; piRNA