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The Institute of Functional Genomics (IGF) is a multidisciplinary research centre which is developing a project focused on the functional genomics of physiological and pathological cellular communications in the fields of neurobiology, endocrinology, oncology and cardiology.
This project is based on a multi-scale strategy from 'molecule to systems' and combines structural, biochemical, genetic, epigenetic, omics, physiological and behavioural studies. A major effort is paid to the development of single-cell studies through multiple dimensions and multi-omic approaches, that are necessary to address the complexity of life.
The project of IGF is increasingly based on translational research, promoted by the recruitment of teams of clinicians from different fields (neurovascular, diabetology, neuro-oncology and psychiatry). The objective is to identify new mechanisms and concepts in the field of cellular communications, in order to develop new therapeutic strategies and diagnostic tools.
STOP CODON READTHROUGH: FROM BASIC RESEARCH TO THERAPEUTIC APPLICATION
NAMY OLIVIER
Institut de Biologie Intégrative de la Cellule (I2BC), Orsay
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 to screen >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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