title: The exon junction complex controls transposable element activity by ensuring faithful splicing of the piwi transcript.
abstract: The exon junction complex (EJC) is a highly conserved ribonucleoprotein complex that binds RNAs during splicing and remains associated with them following export to the cytoplasm. While the role of this complex in mRNA localization, translation, and degradation has been well characterized, its mechanism of action in splicing a subset of Drosophila and human transcripts remains to be elucidated. Here, we describe a novel function for the EJC and its splicing subunit, RnpS1, in preventing transposon accumulation in both Drosophila germline and surrounding somatic follicle cells. This function is mediated specifically through the control of piwi transcript splicing, where, in the absence of RnpS1, the fourth intron of piwi is retained. This intron contains a weak polypyrimidine tract that is sufficient to confer dependence on RnpS1. Finally, we demonstrate that RnpS1-dependent removal of this intron requires splicing of the flanking introns, suggesting a model in which the EJC facilitates the splicing of weak introns following its initial deposition at adjacent exon junctions. These data demonstrate a novel role for the EJC in regulating piwi intron excision and provide a mechanism for its function during splicing.
authors.affiliation: Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA; Howard Hughes Medical Institute.
authors.forename: Colin D
authors.initials: CD
authors.lastname: Malone
authors.affiliation: Institute of Molecular Biology (IMB), 55128 Mainz, Germany;
authors.forename: Claire
authors.initials: C
authors.lastname: Mestdagh
authors.affiliation: Institute of Molecular Biology (IMB), 55128 Mainz, Germany;
authors.forename: Junaid
authors.initials: J
authors.lastname: Akhtar
authors.affiliation: Institute of Molecular Biology (IMB), 55128 Mainz, Germany;
authors.forename: Nastasja
authors.initials: N
authors.lastname: Kreim
authors.affiliation: Institute of Molecular Biology (IMB), 55128 Mainz, Germany;
authors.forename: Pia
authors.initials: P
authors.lastname: Deinhard
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Sachidanandam
authors.affiliation: Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA;
authors.forename: Jessica
authors.initials: J
authors.lastname: Treisman
authors.affiliation: Institute of Molecular Biology (IMB), 55128 Mainz, Germany; j.roignant@imb-mainz.de.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Roignant
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism*; D004251:DNA Transposable Elements / Q000502:physiology*; D018076:DNA, Complementary / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D007438:Introns / Q000235:genetics; D009154:Mutation; D010053:Ovary / Q000166:cytology / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D012326:RNA Splicing; D012261:Ribonucleoproteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D060565:Argonaute Proteins; D004251:DNA Transposable Elements; D018076:DNA, Complementary; D029721:Drosophila Proteins; D021122:Protein Subunits; D012261:Ribonucleoproteins; C116498:piwi protein, Drosophila
keywords: AGO3; EJC; Piwi; piRNA; splicing; transposon
references.citation: Nucleic Acids Res. 2011 Nov;39(21):e141
references.pmid: 21890899
references.citation: Mol Cell Biol. 2012 Mar;32(5):954-67
references.pmid: 22203037
references.citation: Genes Dev. 1993 Nov;7(11):2194-205
references.pmid: 8224846
references.citation: EMBO Rep. 2009 Aug;10(8):810-6
references.pmid: 19648957
references.citation: Genes Dev. 2011 Dec 1;25(23):2502-12
references.pmid: 22156210
references.citation: Mol Cell. 2013 Jun 6;50(5):749-61
references.pmid: 23665227
references.citation: Science. 2008 Nov 28;322(5906):1387-92
references.pmid: 19039138
references.citation: Cell. 2009 May 1;137(3):522-35
references.pmid: 19395010
references.citation: PLoS Biol. 2009 May 26;7(5):e1000120
references.pmid: 19478851
references.citation: Nucleic Acids Res. 1989 Oct 25;17(20):8159-69
references.pmid: 2510128
references.citation: Cell. 2012 Nov 9;151(4):750-764
references.pmid: 23084401
references.citation: RNA. 2009 Oct;15(10):1896-908
references.pmid: 19656867
references.citation: Cell. 2013 Mar 14;152(6):1252-69
references.pmid: 23498935
references.citation: Mol Cell Biol. 2013 Jan;33(2):444-56
references.pmid: 23149939
references.citation: Chromosoma. 2013 Dec;122(6):465-74
references.pmid: 23912688
references.citation: Curr Biol. 1997 Jul 1;7(7):468-78
references.pmid: 9210377
references.citation: Biochem J. 2009 Jan 1;417(1):15-27
references.pmid: 19061484
references.citation: Cell. 2010 Oct 15;143(2):251-62
references.pmid: 20946983
references.citation: Mol Cell. 2013 Jun 6;50(5):736-48
references.pmid: 23665228
references.citation: Genes Dev. 2013 Feb 15;27(4):390-9
references.pmid: 23392610
references.citation: Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21313-8
references.pmid: 23236153
references.citation: Nat Methods. 2008 Oct;5(10):877-9
references.pmid: 18806792
references.citation: Mol Cell Biol. 2004 Feb;24(3):1174-87
references.pmid: 14729963
references.citation: Wiley Interdiscip Rev RNA. 2013 Jan-Feb;4(1):49-60
references.pmid: 23044818
references.citation: Development. 1997 Aug;124(16):3197-207
references.pmid: 9272960
references.citation: Nat Struct Mol Biol. 2012 Mar 04;19(4):378-86
references.pmid: 22388736
references.citation: Genetics. 2004 Mar;166(3):1313-21
references.pmid: 15082550
references.citation: RNA. 2007 Nov;13(11):1911-22
references.pmid: 17872506
references.citation: Dev Biol. 2013 Mar 15;375(2):172-81
references.pmid: 23333945
references.citation: Nat Struct Mol Biol. 2012 Oct;19(10):983-90
references.pmid: 22961380
references.citation: Cell. 1997 May 2;89(3):357-64
references.pmid: 9150135
references.citation: Dev Biol. 2012 Dec 1;372(1):103-10
references.pmid: 22944195
references.citation: Nat Struct Mol Biol. 2004 Apr;11(4):346-51
references.pmid: 15034551
references.citation: RNA. 1996 Jul;2(7):641-51
references.pmid: 8756407
references.citation: Genes Dev. 2002 Nov 1;16(21):2733-42
references.pmid: 12414724
references.citation: Proc Natl Acad Sci U S A. 1981 Oct;78(10):6096-100
references.pmid: 6171811
references.citation: J Cell Biol. 2002 Nov 25;159(4):579-88
references.pmid: 12438415
references.citation: Dev Biol. 2007 Aug 15;308(2):507-19
references.pmid: 17628520
references.citation: RNA. 2010 Dec;16(12):2442-54
references.pmid: 20966198
references.citation: RNA Biol. 2011 Jan-Feb;8(1):24-9
references.pmid: 21289489
references.citation: Development. 2000 Feb;127(3):503-14
references.pmid: 10631171
references.citation: Cell. 2007 Mar 23;128(6):1089-103
references.pmid: 17346786
references.citation: Cell. 2011 Jan 7;144(1):16-26
references.pmid: 21215366
references.citation: Dev Cell. 2006 Feb;10(2):167-76
references.pmid: 16459296
references.citation: RNA. 2012 Aug;18(8):1446-57
references.pmid: 22753781
references.citation: Cell. 2012 Nov 9;151(4):871-884
references.pmid: 23141543
references.citation: EMBO J. 2000 Dec 15;19(24):6860-9
references.pmid: 11118221
references.citation: Nat Neurosci. 2010 May;13(5):551-8
references.pmid: 20364144
references.citation: Genes Dev. 2013 Feb 15;27(4):400-12
references.pmid: 23392609
references.citation: Genome Biol. 2010;11(10):R106
references.pmid: 20979621
references.citation: Curr Biol. 2006 Oct 10;16(19):1884-94
references.pmid: 16949822
references.citation: Mol Cell Biol. 2008 Apr;28(8):2549-58
references.pmid: 18250153
references.citation: Nat Struct Mol Biol. 2005 Oct;12(10):861-9
references.pmid: 16170325
references.citation: J Cell Sci. 2006 Jul 1;119(Pt 13):2635-41
references.pmid: 16787944
references.citation: Dev Cell. 2007 Jan;12(1):45-55
references.pmid: 17199040
references.citation: Adv Exp Med Biol. 2007;623:212-23
references.pmid: 18380349
references.citation: Trends Genet. 2010 Dec;26(12):499-509
references.pmid: 20934772
references.citation: EMBO J. 2010 Oct 6;29(19):3301-17
references.pmid: 20818334
references.citation: Nat Methods. 2012 Mar 04;9(4):357-9
references.pmid: 22388286
references.citation: Science. 1991 Jun 28;252(5014):1823-8
references.pmid: 2063195
references.citation: Genes Dev. 2010 Nov 1;24(21):2343-64
references.pmid: 21041405
references.citation: Curr Biol. 2013 Aug 5;23(15):1442-8
references.pmid: 23891114
references.citation: Nat Struct Mol Biol. 2012 Nov;19(11):1124-31
references.pmid: 23085716
references.citation: EMBO J. 2001 Sep 3;20(17):4987-97
references.pmid: 11532962
references.citation: Nature. 1999 Sep 9;401(6749):168-73
references.pmid: 10490026
references.citation: Genes Dev. 2010 Nov 15;24(22):2499-504
references.pmid: 20966049
references.citation: Cell Rep. 2012 Sep 27;2(3):454-61
references.pmid: 22959432
references.citation: Genes Dev. 2001 Nov 1;15(21):2886-99
references.pmid: 11691839
references.citation: Mol Cell Biol. 2003 Apr;23(8):2981-90
references.pmid: 12665594
references.citation: Cell. 2006 Aug 25;126(4):713-25
references.pmid: 16923391
references.citation: Science. 2007 Mar 16;315(5818):1587-90
references.pmid: 17322028
references.citation: Nucleic Acids Res. 2001 Feb 15;29(4):886-94
references.pmid: 11160920
references.citation: Development. 2001 Jul;128(14):2823-32
references.pmid: 11526087
references.citation: Mol Cell. 2012 Sep 28;47(6):954-69
references.pmid: 22902557
references.citation: Cell. 2010 Oct 15;143(2):238-50
references.pmid: 20946982
references.citation: Genome Res. 2012 Oct;22(10):2008-17
references.pmid: 22722343
references.citation: Genome Biol. 2013 Apr 25;14(4):R36
references.pmid: 23618408
references.citation: Cold Spring Harb Symp Quant Biol. 2006;71:171-80
references.pmid: 17381294
references.citation: Development. 1996 May;122(5):1631-9
references.pmid: 8625849
references.citation: Development. 1997 Jun;124(12):2463-76
references.pmid: 9199372
references.citation: Cell. 1985 Oct;42(3):959-66
references.pmid: 2414014
references.citation: Cell. 2012 Nov 21;151(5):964-80
references.pmid: 23159368
references.citation: RNA. 2005 Dec;11(12):1869-83
references.pmid: 16314458
references.citation: J Biol Chem. 2006 May 5;281(18):12475-84
references.pmid: 16537548
references.citation: Mol Cell. 2013 Jun 6;50(5):762-77
references.pmid: 23665231
references.citation: Genes Dev. 1998 Dec 1;12(23):3715-27
references.pmid: 9851978
references.citation: EMBO J. 1999 Aug 16;18(16):4560-70
references.pmid: 10449421
references.citation: Mol Cell Biol. 2003 Oct;23(20):7363-76
references.pmid: 14517304
references.citation: RNA. 2010 Dec;16(12):2503-15
references.pmid: 20980675
references.citation: Genes Dev. 1994 Feb 1;8(3):363-75
references.pmid: 7906237
references.citation: Genes Dev. 2010 Nov 15;24(22):2493-8
references.pmid: 20966047
references.citation: Curr Biol. 2001 Oct 30;11(21):1666-74
references.pmid: 11696323