A small targeting domain in Ty1 integrase is sufficient to direct retrotransposon integration upstream of tRNA genes

Amna Asif-Laidin (1, 2) , Christine Conesa (3) , Amandine Bonnet (1, 2) , Camille Grison (1, 2) , Indranil Adhya (3) , Rachid Menouni (1, 2) , Hélène Fayol (1, 2) , Noé Palmic (1, 2) , Joël Acker (3) , Pascale Lesage (1, 2)

1 IRSL - Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine ; ex- Institut Universitaire Hématologie-IUH)
2 GenCellDis (U944 / UMR7212) - Génomes, biologie cellulaire et thérapeutiques
3 I2BC - Institut de Biologie Intégrative de la Cellule

Integration of transposable elements into the genome is mutagenic. Mechanisms targeting integrations into relatively safe locations, hence minimizing deleterious consequences for cell fitness, have emerged during evolution. In budding yeast, integration of the Ty1 LTR retrotransposon upstream of RNA polymerase III (Pol III)-transcribed genes requires interaction between Ty1 integrase (IN1) and AC40, a subunit common to Pol I and Pol III. Here, we identify the Ty1 targeting domain of IN1 that ensures (i) IN1 binding to Pol I and Pol III through AC40, (ii) IN1 genome-wide recruitment to Pol I-and Pol III-transcribed genes, and (iii) Ty1 integration only at Pol III-transcribed genes, while IN1 recruitment by AC40 is insufficient to target Ty1 integration into Pol Itranscribed genes. Swapping the targeting domains between Ty5 and Ty1 integrases causes Ty5 integration at Pol III-transcribed genes, indicating that the targeting domain of IN1 alone confers Ty1 integration site specificity.

Mots clés: genome-wide de novo insertion sites; integrase genome-wide occupancy; RNA Polymerases I and III; Ty1 retrotransposon Subject Categories Chromatin; Transcription & Genomics; DNA Replication; Recombination & Repair

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]

Amna Asif-Laidin, Christine Conesa, Amandine Bonnet, Camille Grison, Indranil Adhya, et al.. A small targeting domain in Ty1 integrase is sufficient to direct retrotransposon integration upstream of tRNA genes. EMBO Journal, 2020, 39 (17), pp.e104337. ⟨10.15252/embj.2019104337⟩. ⟨hal-03066142⟩