Société Française de Biochimie et Biologie Moléculaire


Amna ASIF-LAIDIN - SEPTEMBER 2020

Saint-Louis Research Institute, INSERM "A small targeting domain in Ty1 integrase is sufficient to direct retrotransposon integration upstream of tRNA genes." The EMBO Journal 2020 e104337 DOI 10.15252/embj.2019104337
Asif-Laidin A, Conesa C, Bonnet A , Grison C, Adhya I , Menouni R , Fayol H , Palmic N , Acker J and Lesage P

Amna Asif-Laidin, 34, is a post-doctoral fellow in Pascale Lesage et Emmanuelle Fabre team « Genome Biology: From mobile DNA to chromosome dynamics » at the Institut de Recherche Saint-Louis, Paris (Inserm U944, CNRS/Paris Univ UMR7212). During her PhD, carried out under the supervision of Laure Teysset at the Institut of Biology Paris-Seine, she was mainly interested in the repression of transposable elements, by small non-coding RNAs, in the Drosophila germ line. Her post-doctoral work aims at deciphering the molecular bases of Ty1 retrotransposon integration selectivity in the genome of the yeast Saccharomyces cerevisiae. A previous publication described the key role played by the interaction between Ty1 integrase and the AC40 subunit of RNA polymerase III (Pol III) in Ty1 integration preference upstream of Pol III-transcribed genes. In the selected publication, Amna Asif-Laidin and co-workers have identified six consecutive amino acids of Ty1 integrase that are necessary for the interaction with AC40 and shown that this short domain allows the recruitment of Ty1 integrase to all the genes transcribed by Pol I and Pol III because AC40 is common to both polymerases. However, Ty1 integration only occurs at Pol III-transcribed genes, suggesting the intervention of additional factors (chromatin or Pol III specific co-factors) in Ty1 integration selectivity. The study also shows how this short amino acid sequence is sufficient to redirect integration of a chimeric retrotransposon to Pol IIItranscribed genes.

Contact

Genome Biology (GeBi) TeamGenomes and Cell Biology of Diseases Lab
INSERM U944, CNRS UMR7212,
Institut de Recherche Saint-Louis

1 avenue Claude Vellefaux

750010 Paris Cedex 10

FRANCE

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Article Summury:

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 I-transcribed 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.