Development of a next-generation of non-coding RNA-based therapies for genetic diseases

PI:

Gabriella Viero

Email:

gabriella.viero@cnr.it

Affiliation:

Institute of Biophysics - CNR

ORCID:

0000-0002-6755-285X

RNA metabolism at large, and translation in particular, are increasingly recognized as defective hubs in untreatable conditions such as cancer and neurodegenerative diseases, from Alzheimer and Parkinson to Muscular Dystrophies. 
Ribosomes are the core of translation, which is the most energy consuming process in cells, with rRNA and tRNAs draining 80-90% of all transcriptional events. Ribosome composition is not fixed and uniform, but heterogeneous and modulated at the level of ribosomal protein composition, ribosome associated proteins, rRNA variants, post-translational or post-transcriptional modifications.  Based on our published and unpublished results about ribosome heterogeneity and Spinal Muscular Atrophy, we will leverage this ribosome- and heterogeneity-based mechanistic model of disease pathogenesis to foster the discovery and pre-clinical development of a new generation of RNA-based therapies and biomarkers.

Relevant Publications
2023

  1. Brina D, Ponzoni A, Troiani M, Calì B, Pasquini E, Attanasio G, Mosole S, Mirenda M, D’Ambrosio M, Colucci M, Guccini I, Revandkar A, Alajati A, Tebaldi T, Donzel D, Lauria F, Parhizgari N, Valdata A, Maddalena M, Calcinotto A, Bolis M, Rinaldi A, Barry S, Rüschoff JH, Sabbadin M, Sumanasuriya S, Crespo M, Sharp A, Yuan W, Grinu M, Boyle A, Miller C, Trotman L, Delaleu N, Fassan M, Moch H, Viero G, de Bono J, Alimonti A. The Akt/mTOR and MNK/eIF4E pathways rewire the prostate cancer translatome to secrete HGF, SPP1 and BGN and recruit suppressive myeloid cells. Nat Cancer. 2023 Aug;4(8):1102-1121. doi: 10.1038/s43018-023-00594-z. Epub 2023 Jul 17. PMID: 37460872



  2. Paganin M, Tebaldi T, Lauria F, Viero G. Visualizing gene expression changes in time, space, and single cells with expressyouRcell. iScience. 2023 May 11;26(6):106853. doi: 10.1016/j.isci.2023.106853. PMID: 37250782



  3. Cella F, Perrino G, Tedeschi F, Viero G, Bosia C, Stan GB, Siciliano V. MIRELLA: a mathematical model explains the effect of microRNA-mediated synthetic genes regulation on intracellular resource allocation. Nucleic Acids Res. 2023 Apr 24;51(7):3452-3464.



  4. Rossi S, Di Salvio M, Balì M, De Simone A, Apolloni S, D’Ambrosi N, Arisi I, Cipressa F, Cozzolino M, Cestra G. C9orf72 Toxic Species Affect ArfGAP-1 Function. Cells. 2023 Aug 5;12(15):2007. doi: 10.3390/cells12152007. PMID: 37566088 

2022

  1. Negro S, Lauria F, Stazi M, Tebaldi T, D’Este G, Pirazzini M, Megighian A, Lessi F, Mazzanti CM, Sales G, Romualdi C, Fillo S, Lista F, Sleigh JN, Tosolini AP, Schiavo G, Viero G, Rigoni M. Hydrogen peroxide induced by nerve injury promotes axon regeneration via connective tissue growth factor. Acta Neuropathol Commun. 2022 Dec 25;10(1):189. doi: 10.1186/s40478-022-01495-5. PMID: 36567321 Free PMC article.

  2. Destefanis F, Manara V, Santarelli S, Zola S, Brambilla M, Viola G, Maragno P, Signoria I, Viero G, Pasini ME, Penzo M, Bellosta P. Reduction of nucleolar NOC1 leads to the accumulation of pre-rRNAs and induces Xrp1, affecting growth and resulting in cell competition. J Cell Sci. 2022 Dec 1;135(23):jcs260110. doi: 10.1242/jcs.260110. Epub 2022 Dec 7. PMID: 36314272

  3. Biancon G, Joshi P, Zimmer JT, Hunck T, Gao Y, Lessard MD, Courchaine E, Barentine AES, Machyna M, Botti V, Qin A, Gbyli R, Patel A, Song Y, Kiefer L, Viero G, Neuenkirchen N, Lin H, Bewersdorf J, Simon MD, Neugebauer KM, Tebaldi T, Halene S. Precision analysis of mutant U2AF1 activity reveals deployment of stress granules in myeloid malignancies. Mol Cell. 2022 Mar 17;82(6):1107-1122.e7. doi: 10.1016/j.molcel.2022.02.025.

  4. Del Piano A, Kecman T, Schmid M, Barbieri R, Brocchieri L, Tornaletti S, Firrito C, Minati L, Bernabo P, Signoria I, Lauria F, Gillingwater TH, Viero G, Clamer M. Phospho-RNA sequencing with circAID-p-seq. Nucleic Acids Res. 2022 Feb 28;50(4):e23. doi: 10.1093/nar/gkab1158. PMID: 34850942

  5. Licata NV, Cristofani R, Salomonsson S, Wilson KM, Kempthorne L, Vaizoglu D, D’Agostino VG, Pollini D, Loffredo R, Pancher M, Adami V, Bellosta P, Ratti A, Viero G, Quattrone A, Isaacs AM, Poletti A, Provenzani A. C9orf72 ALS/FTD dipeptide repeat protein levels are reduced by small molecules that inhibit PKA or enhance protein degradation. EMBO J. 2022 Jan 4;41(1):e105026. doi: 10.15252/embj.2020105026. Epub 2021 Nov 18. PMID: 34791698 

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