GIULIA BUONAIUTO

Dottoressa di ricerca

ciclo: XXXVI


relatore: Monica Ballarino

Titolo della tesi: Evolutionary conservation of lncRNAs-mediated epigenetic circuitries in cardiac development and pathologies

Tissue-specific long non-coding RNAs (lncRNA) play essential functions in the regulation of cell proliferation and differentiation. Their dysregulation was often linked with neuromuscular and cardiovascular diseases, although the knowledge concerning their modes of action is still far from complete. Among them, nuclear lncRNAs are generally associated with chromatin, where they were shown to contribute to the formation of higher-order chromatin structures (Statello et al., 2021). This is the case of Charme, an abundant and highly conserved lncRNA previously identified in my host lab (Ballarino et al., 2015) and specifically expressed in skeletal myotubes and cardiomyocytes (CM) (Ballarino et al., 2018). My thesis work starts with the observation that in mice the functional loss of the nuclear Charme activities impacts on myogenic differentiation and triggers cardiac remodeling (Desideri et al., 2020). With this knowledge, we aimed to deeply examine the function of the lncRNA in heart development and to characterize its role from an evolutionary perspective, in both the murine and human cardiac biology. In particular, we found that, in mice, the nuclear isoform of Charme (pCharme) acts as an “architect” lncRNA by supervising the chromatin localization of MATR3, a DNA/RNA-binding protein whose mutation has been linked to neuromuscular and cardiovascular diseases. Specifically, in the nucleus, pCharme and MATR3 form ribonucleoprotein condensates that are crucial for the developmental expression of genes involved in the regulation of CMs proliferation/maturation balance. Disruption of these condensates in CharmeKO animals causes a substantial remodeling of the cardiac muscle. Intriguingly, we also found that the human syntenic gene, hsCharme, shares several features and a similar tissue specificity with its murine counterpart. Using the highly adaptable IPSCs system, we could observe that, in the nucleus, the lncRNA plays a conserved role in sustaining human CM maturation. Finally, we found that in human the expression of hsCharme was significantly altered in different types of cardiomyopathies. Since the World Health Organization classify cardiomyopathies among the most prevalent and fatal diseases in humans, understanding the role that hsCharme plays in a pathological context could be extremely important, especially in cases when a clear genetic cause was not identified, as it holds potential as a novel therapeutic tool.

Produzione scientifica

11573/1723044 - 2024 - From mouse to human: how RNA epigenetic influences cardiomyocytes maturation to prevent cardiac hyperplasia
Buonaiuto, Giulia; Palma, Alessandro; Simula, Marco; Storari, Giulio; Durante, Daniele; Santini, Tiziana; Ballarino, Monica - 04d Abstract in atti di convegno
congresso: EMBO workshop 2024. The new cardiobiology (Heidelberg, Germany)
libro: Abstract book - ()

11573/1723129 - 2024 - The lncRNA Charme, an evolutionary conserved regulator of muscle differentiation and pathology
Buonaiuto, Giulia; Simula, Marco; Durante, Daniele; Storari, Giulio; Palma, Alessandro; Laneve, Pietro; Ballarino, Monica - 04d Abstract in atti di convegno
congresso: Non-coding RNA World 2024: Exploring Mechanisms, Designing Medicines (Basel, Switzerland)
libro: Abstract Book - ()

11573/1723045 - 2024 - The nuclear lncRNA Charme plays an evolutionarily conserved role in the epigenetic regulation of muscle differentiation
Buonaiuto, Giulia; Storari, Giulio; Palma, Alessandro; Simula, Marco; Durante, Daniele; Laneve, Pietro; Ballarino, Monica - 04d Abstract in atti di convegno
congresso: The time of Molecular Biology: development, homeostasis and aging, SIBBM 2024 (Trento, Italy)
libro: Abstract Book - ()

11573/1723128 - 2024 - Long noncoding RNAs at the interface between muscles and nerves”
Simula, Marco; Durante, Daniele; Buonaiuto, Giulia; Storari, Giulio; Tollis, Paolo; Laneve, Pietro; Ballarino, Monica - 04d Abstract in atti di convegno
congresso: 21st IIM meeting: From muscle physiology to pathogenesis and therapies of neuromuscular disease (Assisi, Italy)
libro: Abstract book - ()

11573/1723099 - 2024 - Neuromuscular interplay and lncRNAs: a synaptic liaison
Simula, Marco; Tollis, Paolo; Buonaiuto, Giulia; Palma, Alessandro; Durante, Daniele; Storari, Giulio; Laneve, Pietro; Ballarino, Monica - 04d Abstract in atti di convegno
congresso: CSH 2024: Regulatory & Non-Coding RNAs (Cold Spring Harbour, USA)
libro: Abstract book - ()

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)

11573/1696990 - 2023 - The role of charme in the phenotype and function of resident cardiac mesenchymal stromal cells
Floris, E; Picchio, V; Cozzolino, C; Taliani, V; Buonaiuto, G; Nicoletti, C; Ballarino, M; Chimenti, I; Pagano, F - 01h Abstract in rivista
rivista: EUROPEAN HEART JOURNAL (-London : Harcourt -Oxford : Oxford University Press) pp. - - issn: 1522-9645 - wos: WOS:001115619405081 (0) - scopus: (0)

11573/1674499 - 2023 - The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the developing heart
Taliani, Valeria; Buonaiuto, Giulia; Desideri, Fabio; Setti, Adriano; Santini, Tiziana; Galfrè, Silvia; Schirone, Leonardo; Mariani, Davide; Frati, Giacomo; Valenti, Valentina; Sciarretta, Sebastiano; Perlas, Emerald; Nicoletti, Carmine; Musarò, Antonio; Ballarino, Monica - 01a Articolo in rivista
rivista: ELIFE (Cambridge: eLife Sciences Publications) pp. - - issn: 2050-084X - wos: WOS:000954333700001 (6) - scopus: 2-s2.0-85150666103 (6)

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 (5)

11573/1477955 - 2021 - Epigenetic regulation of Wnt7b expression by the cis-acting long noncoding RNA Lnc-Rewind in muscle stem cells
Cipriano, Andrea; Macino, Martina; Buonaiuto, Giulia; Santini, Tiziana; Biferali, Beatrice; Peruzzi, Giovanna; Colantoni, Alessio; Mozzetta, Chiara; Ballarino, Monica - 01a Articolo in rivista
rivista: ELIFE (Cambridge: eLife Sciences Publications) pp. - - issn: 2050-084X - wos: WOS:000613733100001 (21) - scopus: 2-s2.0-85100012617 (25)

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 (24)

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 - ()

11573/1487112 - 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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