ADRIANO SETTI

Dottore di ricerca

ciclo: XXXV


relatore: Julie Martone
co-supervisore: Alessandro Rosa

Titolo della tesi: Role of RNA interactions in neuro-muscular development and pathology

The role of RNA interactions is crucial during complex processes such as cell differentiation in which many layers of molecular regulatory mechanism are orchestrated to promote the progression of developmental stages. In particular we have characterized the molecular mechanism of two lncRNAs: we demonstrated that lncSMaRT is able to base pairs with its targets mRNAs, Mlx y and Spire1, mediating their translational repression and thus promoting murine skeletal muscle differentiation; moreover, we have described the functions of the multiple elements generated by the complex MN2 locus: two miRNAs (miR-384-5p and miR-325-3p) and a cytoplasmic lncRNA lncMN2-203 that synergistically cooperate to favor motor neurogenesis. Moreover, the role of RNA interaction is often deregulated in pathological context. In neuro-muscular diseases we have characterized the role of RNA interactions focusing on Rhabdomyosarcoma and the motoneuron disease Amyotrophic Lateral Sclerosis (ALS). Indeed, we demonstrated that in Rhabdomyosarcoma there is an augmented production of a class of peculiar lncRNAs, the covalently closed circular RNAs. Little is known about their biogenesis and alteration in cancer. We demonstrated that YTHDC1, the reader of the RNA epitranscriptomic modification N6 methyladenosine and the RNA helicase DDX5 are able to act in complex to regulate this process in this cancer type. Furthermore, the role of RNA interactions is pivotal especially in the generation of membrane-less organelles that have often crucial implications in neurodegenerative diseases such as ALS. I have studied the interplay between the ALS associated FUS mutation P525L and the cytoplasmic membrane-less organelles Stress Granules (SGs). These condensates are generated in condition of oxidative stress and are important for storage of mRNAs when translation is stalled. We have characterized the first SG transcriptome in human neural system, and we have found that in presence of mutant FUS their physical properties and RNA composition are altered. Finally, we have studied the role of m6A in regulating these membrane-less organelles.

Produzione scientifica

  • 11573/1677113 - 2023 - The m6A reader YTHDC1 and the RNA helicase DDX5 control the production of rhabdomyosarcoma-enriched circRNAs (01a Articolo in rivista)
    DATTILO, DARIO; DI TIMOTEO, GAIA; SETTI, ADRIANO; GIULIANI, ANDREA; PERUZZI, GIOVANNA; BELTRAN NEBOT, MANUEL; MARIANI, DAVIDE; MOZZETTA, CHIARA; BOZZONI, IRENE
  • 11573/1674499 - 2023 - The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the developing heart (01a Articolo in rivista)
    TALIANI, VALERIA; BUONAIUTO, GIULIA; SETTI, ADRIANO; SANTINI, TIZIANA; SCHIRONE, LEONARDO; FRATI, GIACOMO; SCIARRETTA, SEBASTIANO; NICOLETTI, CARMINE; MUSARO', ANTONIO; BALLARINO, MONICA
  • 11573/1416609 - 2020 - SMaRT lncRNA controls translation of a G-quadruplex-containing mRNA antagonizing the DHX36 helicase (01a Articolo in rivista)
    MARTONE, JULIE; MARIANI, DAVIDE; SETTI, ADRIANO; SHAMLOO, SAMA; COLANTONI, ALESSIO; CAPPARELLI, FRANCESCA; PAIARDINI, ALESSANDRO; DIMARTINO, DACIA; BOZZONI, IRENE
  • 11573/1427982 - 2020 - Trans-generational epigenetic regulation associated with the amelioration of Duchenne Muscular Dystrophy (01a Articolo in rivista)
    MARTONE, JULIE; LISI, MICHELA; CASTAGNETTI, FRANCESCO; ROSA, ALESSANDRO; DI CARLO, VALERIO; SETTI, ADRIANO; MARIANI, DAVIDE; COLANTONI, ALESSIO; SANTINI, TIZIANA; PERONE, LEONARDO; BOZZONI, IRENE
  • 11573/1600938 - 2021 - Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity (01a Articolo in rivista)
    ROSSI, FRANCESCA; BELTRAN NEBOT, MANUEL; DAMIZIA, MICHELA; GRELLONI, CHIARA; COLANTONI, ALESSIO; SETTI, ADRIANO; DI TIMOTEO, GAIA; DATTILO, DARIO; CENTRON BROCO, ALVARO ANASTASIO; NICOLETTI, CARMINE; BOZZONI, IRENE
  • 11573/1610567 - 2022 - Lnc-SMaRT translational regulation of Spire1, a new player in muscle differentiation (01a Articolo in rivista)
    SCALZITTI, SILVIA; MARIANI, DAVIDE; SETTI, ADRIANO; COLANTONI, ALESSIO; LISI, MICHELA; BOZZONI, IRENE; MARTONE, JULIE
  • 11573/1649233 - 2022 - A multifunctional locus controls motor neuron differentiation through short and long noncoding RNAs (01a Articolo in rivista)
    CARVELLI, ANDREA; SETTI, ADRIANO; BISCARINI, SILVIA; COLANTONI, ALESSIO; CAPAUTO, DAVIDE; DI ANGELANTONIO, SILVIA; BALLARINO, MONICA; LANEVE, PIETRO; BOZZONI, IRENE
  • 11573/1671596 - 2023 - A KO mouse model for the lncRNA Lhx1os produces motor neuron alterations and locomotor impairment (01a Articolo in rivista)
    PELLEGRINI, FLAMINIA; PADOVANO, VITTORIO; BISCARINI, SILVIA; SANTINI, TIZIANA; SETTI, ADRIANO; SILENZI, VALENTINA; VITIELLO, ERIKA; MARIANI, DAVIDE; NICOLETTI, CARMINE; TORROMINO, GIULIA; DE LEONIBUS, ELVIRA; MARTONE, JULIE; BOZZONI, IRENE

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