Ribosome readthrough

La presenza di un codone di stop prematuro (mutazione nonsenso) causa la sintesi di una proteina tronca con caratteristiche alterate. L'attività di ricerca è incentrata sullo studio del processo di readthrough, durante il quale il ribosoma introduce un aminoacido “by-passando” il codone di stop prematuro e portando alla sintesi di una proteina a lunghezza normale. Questi studi permettono di dettagliare i determinanti molecolari del readthrough, sia basale che indotto da farmaci.

 

Pubblicazioni:

 

Engineered tRNAs efficiently suppress CDKL5 premature termination codons. Pezzini S, Mustaccia A, Aboa P, Faustini G, Branchini A, Pinotti M, Frasca A, Porter JJ, Lueck JD, Landsberger N.

Sci Rep. 2024 Dec 30;14(1):31791.

doi: 10.1038/s41598-024-82766-0.

 

Translational readthrough at F8 nonsense variants in the factor VIII B domain contributes to residual expression and lowers inhibitor association. Testa MF, Lombardi S, Bernardi F, Ferrarese M, Belvini D, Radossi P, Castaman G, Pinotti M, Branchini A.

Haematologica. 2023 Feb 1;108(2):472-482.

doi: 10.3324/haematol.2022.281279.

 

A recoded view on the F9 p.Cys178Ter pathogenic mechanism. Branchini A, Pinotti M.

Thromb Res. 2020 Mar;187:88-90.

doi: 10.1016/j.thromres.2020.01.016.

 

Translational readthrough of GLA nonsense mutations suggests dominant-negative effects exerted by the interaction of wild-type and missense variants. Lombardi S, Ferrarese M, Marchi S, Pinton P, Pinotti M, Bernardi F, Branchini A.

RNA Biol.2020 Feb;17(2):254-263.

doi: 10.1080/15476286.2019.1676115

 

Missense changes in the catalytic domain of coagulation factor X account for minimal function preventing a perinatal lethal condition. Ferrarese M, Baroni M, Della Valle P, Spiga I, Poloniato A, D'Angelo A, Pinotti M, Bernardi F, Branchini A.

Haemophilia. 2019 Jul;25(4):685-692.

doi: 10.1111/hae.13761.

 

Secretion of wild-type factor IX upon readthrough over F9 pre-peptide nonsense mutations causing hemophilia B. Ferrarese M, Testa MF, Balestra D, Bernardi F, Pinotti M, Branchini A.

Hum Mutat. 2018 May;39(5):702-708.

doi: 10.1002/humu.23404

 

Specific factor IX mRNA and protein features favor drug-induced readthrough over recurrent nonsense mutations. Branchini A, Ferrarese M, Campioni M, Castaman G, Mari R, Bernardi F, Pinotti M.
Blood. 2017 Apr 20;129(16):2303-2307.

doi: 10.1182/blood-2016-09-738641

 

Differential functional readthrough over homozygous nonsense mutations contributes to the bleeding phenotype in coagulation factor VII deficiency. Branchini A, Ferrarese M, Lombardi S, Mari R, Bernardi F, Pinotti M.

J Thromb Haemost. 2016 Oct;14(10):1994-2000.

doi: 10.1111/jth.13443

 

Review e capitoli di libro:

 

Nonsense Mutations in Rare and Ultra-Rare Human Disorders: An Overview. Vitale E, Ricci D, Corrao F, Fiduccia I, Cruciata I, Carollo PS, Branchini A, Lentini L, Pibiri I.

IUBMB Life. 2025 Jun;77(6):e70031.

doi: 10.1002/iub.70031.

 

Advancing therapeutic Strategies for Nonsense-Related Diseases: From Small Molecules to Nucleic Acid-Based Innovations. Ricci D, Cruciata I, Fiduccia I, Vitale E, Corrao F, Branchini A, Carollo PS, Pibiri I, Lentini L.

IUBMB Life. 2025 May;77(5):e70027.

doi: 10.1002/iub.70027.

 

Translation termination codons in protein synthesis and disease. Lombardi S, Testa MF, Pinotti M, Branchini A.

Adv Protein Chem Struct Biol. 2022 Sep; 132:1-48.

doi: 10.1016/bs.apcsb.2022.06.001.

 

Molecular Insights into Determinants of Translational Readthrough and Implications for Nonsense Suppression Approaches. Lombardi S, Testa MF, Pinotti M, Branchini A.

Int J Mol Sci. 2020 Dec 11;21(24):9449.

doi: 10.3390/ijms21249449.

 

Molecular Mechanisms and Determinants of Innovative Correction Approaches in Coagulation Factor Deficiencies. Balestra D, Branchini A.

Int J Mol Sci. 2019 Jun 21;20(12):3036.

doi: 10.3390/ijms20123036.