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Collapse of Germline piRNAs in the Absence of Argonaute3 Reveals Somatic piRNAs in Flies
Chengjian Li 1,9, Vasily V. Vagin 1,9,10, Soohyun Lee 2,5,9, Jia Xu 2,6,9, Shengmei Ma 1, Hualin Xi 5,7, Hervé Seitz 1, Michael D. Horwich 1, Monika Syrzycka 8, Barry M. Honda 8, Ellen L.W. Kittler 3, Maria L. Zapp 3, Carla Klattenhoff 4, Nadine Schulz 4, William E. Theurkauf 4, Zhiping Weng 2,*, and Phillip D. Zamore 1,*
1 Department of Biochemistry and Molecular Pharmacology and Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
2 Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
3 Program in Molecular Medicine and Center for AIDS Research (CFAR), University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
4 Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
5 Bioinformatics Program, Boston University, Boston, MA 02215, USA
6 Biomedical Engineering, Boston University, Boston, MA 02215, USA
7 Computational Sciences Center of Emphasis, Pfizer, Inc., 620 Memorial Drive, Cambridge, MA 02139, USA
8 Molecular Biology and Biochemistry, Simon Fraser University, Burnaby BC V5A 1S6, Canada
* Corresponding author
9 These authors contributed equally to this work
10 Present address: Cold Spring Harbor Laboratories, Cold Spring Harbor, New York 11724, USA Summary
Piwi-interacting RNAs (piRNAs) silence transposons in animal germ cells. piRNAs are thought to derive from long transcripts spanning transposon-rich genomic loci and to direct an autoamplification loop in which an antisense piRNA, bound to Aubergine or Piwi protein, triggers production of a sense piRNA bound to the PIWI protein Argonaute3 (Ago3). In turn, the new piRNA is envisioned to produce a second antisense piRNA. Here, we describe strong loss-of-function mutations in ago3, allowing a direct genetic test of this model. We find that Ago3 acts to amplify piRNA pools and to enforce on them an antisense bias, increasing the number of piRNAs that can act to silence transposons. We also detect a second, Ago3-independent piRNA pathway centered on Piwi. Transposons targeted by this second pathway often reside in the flamenco locus, which is expressed in somatic ovarian follicle cells, suggesting a role for piRNAs beyond the germline. |
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박정수 (Harvard Medical School)
Google (by Soohyun Lee)
Pubmed (by Soohyun Lee)
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