Abstract: Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for the CFTR chloride channel. About 10% of the CFTR gene mutations are "stop" mutations, which generate a Premature Termination Codon (PTC), thus synthesizing a truncated CFTR protein. A way to bypass PTC relies on ribosome readthrough, which is the ri-bosome’s capacity to skip a PTC, thus generating a full-length protein. “TRIDs” are molecules exerting ribosome readthrough; for some, the mechanism of action is still under debate. We in-vestigate a possible mechanism of action (MOA) by which our recently synthesized TRIDs, namely NV848, NV914, and NV930, could exert their readthrough activity by in silico analysis and in vitro studies. Our results suggest a likely inhibition of FTSJ1, a tryptophan tRNA-specific 2’-O-methyltransferase.

Pietro Salvatore Carollo, Marco Tutone, Giulia Culletta, Ignazio Fiduccia, Federica Corrao, Ivana Pibiri, et al. (2023). Investigating the inhibition of FTSJ1 a tryptophan tRNA-specific 2’-O-methyltransferase by NV TRIDs, as a mechanism of readthrough in nonsense mutated CFTR. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 [10.3390/ijms24119609].

Investigating the inhibition of FTSJ1 a tryptophan tRNA-specific 2’-O-methyltransferase by NV TRIDs, as a mechanism of readthrough in nonsense mutated CFTR

Pietro Salvatore Carollo
Formal Analysis
;
Marco Tutone
Formal Analysis
;
Giulia Culletta
Formal Analysis
;
Ignazio Fiduccia
Methodology
;
Federica Corrao
Methodology
;
Ivana Pibiri
Funding Acquisition
;
Maria Grazia Zizzo
Methodology
;
Raffaella Melfi
Methodology
;
Andrea Pace
Writing – Review & Editing
;
Anna Maria Almerico
Penultimo
Data Curation
;
Laura Lentini
Ultimo
Funding Acquisition
2023-06-01

Abstract

Abstract: Cystic Fibrosis (CF) is an autosomal recessive genetic disease caused by mutations in the CFTR gene, coding for the CFTR chloride channel. About 10% of the CFTR gene mutations are "stop" mutations, which generate a Premature Termination Codon (PTC), thus synthesizing a truncated CFTR protein. A way to bypass PTC relies on ribosome readthrough, which is the ri-bosome’s capacity to skip a PTC, thus generating a full-length protein. “TRIDs” are molecules exerting ribosome readthrough; for some, the mechanism of action is still under debate. We in-vestigate a possible mechanism of action (MOA) by which our recently synthesized TRIDs, namely NV848, NV914, and NV930, could exert their readthrough activity by in silico analysis and in vitro studies. Our results suggest a likely inhibition of FTSJ1, a tryptophan tRNA-specific 2’-O-methyltransferase.
1-giu-2023
Settore BIO/18 - Genetica
Settore CHIM/06 - Chimica Organica
Settore CHIM/08 - Chimica Farmaceutica
Pietro Salvatore Carollo, Marco Tutone, Giulia Culletta, Ignazio Fiduccia, Federica Corrao, Ivana Pibiri, et al. (2023). Investigating the inhibition of FTSJ1 a tryptophan tRNA-specific 2’-O-methyltransferase by NV TRIDs, as a mechanism of readthrough in nonsense mutated CFTR. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 24 [10.3390/ijms24119609].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/592653
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