FABIO DESIDERI

Dottore di ricerca

ciclo: XXXII



Titolo della tesi: Investigating the role of Charme: a chromatin-associated IncRNA supervisor of mammals myogenesis

The mammalian genome contains thousands of long non-coding RNAs (lncRNAs), which have been proposed to be fundamental in the regulation of many biological processes. Among them, nuclear lncRNAs are generally associated to chromatin, where they can act as genome architects contributing to the formation or disassembly of 3D structures. Through a high-throughput transcriptome screening, a subset of new polyadenylated and multi-exonic lncRNAs differentially expressed during murine skeletal muscle differentiation in vitro, was identified (Ballarino et al., 2015). In particular, we focused on one candidate, Charme (for Chromatin architect of muscle expression) that is an abundant and highly conserved non-coding transcript specifically required for in vitro myogenesis. Interestingly, Charme ablation in vivo resulted in a very distinct cardiac pathological phenotype in which the morphology of the murine heart is remodelled (Ballarino et al., 2018). In this work, we deepen the study of the Charme mechanism of action by characterizing its protein interactors. Interestingly, we found that the intron retained Charme isoform (pCharme) is able to specifically bind to MATR3 and PTBP1, two proteins involved in nuclear organization and RNA metabolism. Loss of function experiments demonstrate that PTBP1, supported by MATR3, reinforces the nuclear retention and stabilization of pCharme. Reciprocally, the lncRNA is able to function as a guide for MATR3 recognition of its chromatin targets. Consistent with these data, the targeted deletion of intron 1 by CRISPR/Cas9 in a mouse model, induces the delocalization of the mutant pCharme from the chromatin to the cytoplasm, and results in a muscle phenotype similar to what is observed upon knockout of the full-length transcript (Charme -/-) (Ballarino et al., 2018). Finally, to expand our knowledge on the human Charme (hs-Charme), we generated a CRISPR/CAS9 hs-Charme knock out hiPS cell line and found that the human lncRNA could be involved in the control of cell contraction in cardiomyocytes. Overall, our findings unveil new determinants, which contribute to regulate pCharme activities and reinforce the importance of the intimate interplay between pCharme and the chromatin to allow the lncRNA to exert its function.

Produzione scientifica

11573/1717792 - 2024 - CyCoNP lncRNA establishes cis and trans RNA-RNA interactions to supervise neuron physiology
Desideri, Fabio; Grazzi, Alessandro; Lisi, Michela; Setti, Adriano; Santini, Tiziana; Colantoni, Alessio; Proietti, Gabriele; Carvelli, Andrea; Tartaglia, Gian Gaetano; Ballarino, Monica; Bozzoni, Irene - 01a Articolo in rivista
rivista: NUCLEIC ACIDS RESEARCH (Oxford University Press:Journals Department, Great Clarendon Street, Oxford OX2 6DP United Kingdom:011 44 1865 556767, EMAIL: jnlorders@oup.co.uk, INTERNET: http://www.oup.co.uk, Fax: 011 44 1865 267485 Editore precedente: Information Retrieval ltd., London) pp. 1-17 - issn: 0305-1048 - wos: WOS:001265789600001 (0) - scopus: 2-s2.0-85203504480 (0)

11573/1723041 - 2023 - From mouse to human: how RNA epigenetic influences cardiomyocytes maturation
Buonaiuto, Giulia; Palma, Alessandro; Simula, Marco; Desideri, Fabio; Ballarino, Monica - 04d Abstract in atti di convegno
congresso: SIBBM 2023. Beyond Genomics: Next Generation Molecular Biology (Bari)
libro: Abstract book - ()

11573/1690600 - 2023 - Preparation of cardiac extracts from embryonal hearts to capture RNA–protein interactions by CLIP
Buonaiuto, Giulia; Taliani, Valeria; Nicoletti, Carmine; Desideri, Fabio; Ballarino, Monica - 01a Articolo in rivista
rivista: BIO-PROTOCOL ([Sunnyvale, CA] : Bio-protocol LLC, 2011-) pp. - - issn: 2331-8325 - wos: WOS:001104045600004 (0) - scopus: 2-s2.0-85175812537 (0)

11573/1657186 - 2022 - Advances in endogenous RNA pull-down: A straightforward dextran sulfate-based method enhancing RNA recovery
Desideri, Fabio; D’Ambra, Eleonora; Laneve, Pietro; Ballarino, Monica - 01a Articolo in rivista
rivista: FRONTIERS IN MOLECULAR BIOSCIENCES (Lausanne : Frontiers Media S.A., 2014-) pp. - - issn: 2296-889X - wos: WOS:000879858100001 (5) - scopus: 2-s2.0-85141435654 (5)

11573/1570590 - 2021 - Muscle regeneration and RNA: new perspectives for ancient molecules
Buonaiuto, Giulia; Desideri, Fabio; Taliani, Valeria; Ballarino, Monica - 01a Articolo in rivista
rivista: CELLS (Basel: mdpi-Molecular Diversity Preservation International) pp. 2512- - issn: 2073-4409 - wos: WOS:000713414300001 (5) - scopus: 2-s2.0-85115409677 (4)

11573/1473622 - 2020 - Intronic determinants coordinate charme lncRNA nuclear activity through the interaction with MATR3 and PTBP1
Desideri, F.; Cipriano, A.; Petrezselyova, S.; Buonaiuto, G.; Santini, T.; Kasparek, P.; Prochazka, J.; Janson, G.; Paiardini, A.; Calicchio, A.; Colantoni, A.; Sedlacek, R.; Bozzoni, I.; Ballarino, M. - 01a Articolo in rivista
rivista: CELL REPORTS (Elsevier B.V. Cambridge MA: Cell Press) pp. - - issn: 2211-1247 - wos: WOS:000601399100024 (22) - scopus: 2-s2.0-85098200912 (23)

11573/1343555 - 2020 - Non-coding RNAs shaping muscle
Martone, Julie; Mariani, Davide; Desideri, Fabio; Ballarino, Monica - 01a Articolo in rivista
rivista: FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (Lausanne : Frontiers Media S.A., 2013-) pp. - - issn: 2296-634X - wos: WOS:000517179100001 (23) - scopus: 2-s2.0-85079781450 (29)

11573/1487089 - 2019 - Characterization of the human long noncoding RNA Charme
Buonaiuto, Giulia; Cipriano, Andrea; Desideri, Fabio; Tita, Rossella; Santini, Tiziana; Nicoletti, Carmine; Calicchio, Alessandro; Carrieri, Claudia; Musaro', Antonio; O’ Carroll, Donal; Bozzoni, Irene; Ballarino, Monica - 04f Poster
congresso: 8th international course on non-coding genome, Institut Curie 2019 (Paris; France)
libro: 8th international course on non-coding genome, Abstract book - ()

11573/1487111 - 2019 - Deciphering the long noncoding RNAs language in myogenesis: a comprehensive glimpse on Charme
Buonaiuto, Giulia; Desideri, Fabio; Taliani, Valeria; Santini, Tiziana; Colantoni, Alessio; Perlas, Emerald; Nicoletti, Carmine; Musaro', Antonio; Bozzoni, Irene; Ballarino, Monica - 04f Poster
congresso: ShareScience, La Sapienza University 2019 (Rome; Italy)
libro: Abstract book - ()

11573/1487116 - 2018 - Non-coding regulation of myogenic chromatin
Ballarino, Monica; Cipriano, Andrea; Desideri, Fabio; Santini, Tiziana; Nicoletti, Carmine; Calicchio, Alessandro; Buonaiuto, Giulia; Morlando, Mariangela; Musaro', Antonio; Bozzoni, Irene - 04d Abstract in atti di convegno
congresso: SIBBM, 2018 (Rome; Italy)
libro: Abstract book - ()

11573/1145703 - 2018 - Deficiency in the nuclear long noncoding RNACharme causes myogenic defects and heart remodeling in mice
Ballarino, Monica; Cipriano, Andrea; Tita, Rossella; Santini, Tiziana; Desideri, Fabio; Morlando, Mariangela; Colantoni, Alessio; Carrieri, Claudia; Nicoletti, Carmine; Musarò, Antonio; Carroll, Dònal O’; Bozzoni, Irene - 01a Articolo in rivista
rivista: EMBO JOURNAL (attuale: NATURE PUBLISHING GROUP, 345 PARK AVENUE SOUTH, NEW YORK, USA, NY, 10010-1707 Precedente: Oxford University Press:Journals Department, Great Clarendon Street, Oxford OX2 6DP United Kingdom:011 44 1865 556767, EMAIL: jnlorders@oup.co.uk, INTERNET: http://www.oup.co.uk, Fax: 011 44 1865 267485) pp. 1-16 - issn: 0261-4189 - wos: WOS:000444804700011 (59) - scopus: 2-s2.0-85052850541 (60)

11573/1487112 - 2018 - The lncRNA Charme regulates skeletal muscle differentiation and heart development
Cipriano, Andrea; Desideri, Fabio; Tita, Rossella; Santini, Tiziana; Nicoletti, Carmine; Calicchio, Alessandro; Buonaiuto, Giulia; Musaro', Antonio; O’ Carroll, Donal; Bozzoni, Irene; Ballarino, Monica - 04d Abstract in atti di convegno
congresso: Muscle development, regeneration and disease, 2018 (Berlin; Germany)
libro: Abstract book - ()

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