Retrotransposons. An RNA polymerase III subunit determines sites of retrotransposon integration.
Mobile genetic elements are ubiquitous. Their integration site influences genome stability and gene expression. The Ty1 retrotransposon of the yeast Saccharomyces cerevisiae integrates upstream of RNA polymerase III (Pol III)-transcribed genes, yet the primary determinant of target specificity has remained elusive. Here we describe an interaction between Ty1 integrase and the AC40 subunit of Pol III and demonstrate that AC40 is the predominant determinant targeting Ty1 integration upstream of Pol III-transcribed genes. Lack of an integrase-AC40 interaction dramatically alters target site choice, leading to a redistribution of Ty1 insertions in the genome, mainly to chromosome ends. The mechanism of target specificity allows Ty1 to proliferate and yet minimizes genetic damage to its host.
Université Paris Diderot, Sorbonne Paris Cité, INSERM U944, CNRS UMR 7212, Institut Universitaire d'Hématologie, Hôpital St. Louis, 75010 Paris, France. Department CASER Conservatoire National des Arts et Métiers (Cnam), 75003 Paris, France.
Antoine
A
Bridier-Nahmias
Université Paris Diderot, Sorbonne Paris Cité, INSERM U944, CNRS UMR 7212, Institut Universitaire d'Hématologie, Hôpital St. Louis, 75010 Paris, France.
Aurélie
A
Tchalikian-Cosson
Department of Genetics, Cell Biology and Development and Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA. Minnesota Supercomputing Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Joshua A
JA
Baller
Université Paris Diderot, Sorbonne Paris Cité, INSERM U944, CNRS UMR 7212, Institut Universitaire d'Hématologie, Hôpital St. Louis, 75010 Paris, France.
Rachid
R
Menouni
Université Paris Diderot, Sorbonne Paris Cité, INSERM U944, CNRS UMR 7212, Institut Universitaire d'Hématologie, Hôpital St. Louis, 75010 Paris, France.
Hélène
H
Fayol
IBiTec-S, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), CNRS, Université Paris-Sud, CP 22, CEA-Saclay, 91191 Gif-sur-Yvette, France.
Amando
A
Flores
Université Paris Diderot, Sorbonne Paris Cité, INSERM U944, CNRS UMR 7212, Institut Universitaire d'Hématologie, Hôpital St. Louis, 75010 Paris, France. Department CASER Conservatoire National des Arts et Métiers (Cnam), 75003 Paris, France.
Ali
A
Saïb
IBiTec-S, Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), CNRS, Université Paris-Sud, CP 22, CEA-Saclay, 91191 Gif-sur-Yvette, France.
Michel
M
Werner
Department of Genetics, Cell Biology and Development and Center for Genome Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Daniel F
DF
Voytas
Université Paris Diderot, Sorbonne Paris Cité, INSERM U944, CNRS UMR 7212, Institut Universitaire d'Hématologie, Hôpital St. Louis, 75010 Paris, France. pascale.lesage@inserm.fr.
Pascale
P
Lesage
D015825:Chromosomes, Fungal / Q000235:genetics; D012321:DNA-Directed RNA Polymerases / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D012320:RNA Polymerase III / Q000378:metabolism*; D012343:RNA, Transfer / Q000235:genetics; D018626:Retroelements / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D018626:Retroelements; D029702:Schizosaccharomyces pombe Proteins; D012343:RNA, Transfer; D019426:Integrases; C403180:rpc40 protein, S pombe; D012321:DNA-Directed RNA Polymerases; D012320:RNA Polymerase III