CIRI seminar: Dr. Olivier NAMY
Date / Heure
Date(s) - 23/10/2019
11 h 00 min - 12 h 00 min
Dr. Olivier NAMY (Institut de Biologie Intégrative de la Cellule CNRS UMR9198 – Orsay): “ Stop codon readthrough : from basic research to therapeutic application ”
Nonsense mutations, generating premature termination codons account for 10% to 30% of the mutations found in human genetic diseases. Nonsense translational suppression, induced by small molecules including gentamicin and G418, has been suggested as a potential therapy to counteract the deleterious effects of nonsense mutations in several genetic diseases and cancers.
This therapeutic approach is currently limited by the small number of available drugs promoting stop codon readthrough and by our lack of knowledge about tRNAs that are able to decode stop codons. We performed an HTS of >17000 compounds to identify new readthrough inducers. In parallel we addressed the role of modifications found in the anticodon loop of several tRNAs on their ability to recognize the stop codon. We show that almost systematically, the modification confers to these tRNAs the ability to act as a near cognate tRNAs on stop codons, without noticeable impact on their ability to decode cognate or near-cognate sense codons. These findings reveal an important role of modifications for tRNA decoding.
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