PAOLO TOLLIS

Dottore di ricerca

ciclo: XXXV



Titolo della tesi: Decoding the role of the lncRNA HOTAIRM1 in human motor neurons

The mammalian genome produces thousands of long non-coding RNAs (lncRNAs), which have been demonstrated to be fundamental in the control of many biological processes. These molecules play a crucial role in the multilayered regulation of physiological and disease-related gene expression programs, showing to have significant implications in shaping central nervous system (CNS) complexity. Neuronal differentiation is a timely and spatially regulated process, relying on precisely orchestrated gene expression control. The coordinated activity of transcription factors and non-coding RNAs (ncRNAs), organized in intricate regulatory networks, drives cell fate specification ensuring correct and specific neuronal functions. We previously described, at both the molecular and functional level, the lncRNA nHOTAIRM1 as a neuronal-enriched transcript, that is upregulated during in vitro neuronal differentiation and highly expressed in post-mitotic motor neurons (MNs). We demonstrated that the nuclear nHOTAIRM1, even if much less abundant than its cytoplasmic counterpart, is involved in the achievement of correct neuronal differentiation timing as an epigenetic regulator of NEUROG2 expression. Remarkably, among all human brain tissues, nHOTAIRM1 is specifically expressed in the spinal cord. Consistently, we found that nHOTAIRM1 accumulates in MN-enriched ventral spinal cord lineages differentiated from human induced pluripotent stem cells (iPSCs). All this evidence prompted us to further investigate the role of the highly expressed nHOTAIRM1 specifically on MN generation and/or function, to ultimately determine whether its deregulation affects MN differentiation and activity. To experimentally address these questions, here we applied a genome editing-based loss-of-function approach to a model system that efficiently recapitulates spinal MN differentiation, and we identified key nHOTAIRM1 target genes implicated in MN maturation, morphology and activity. Our findings allowed us to conclude that nHOTAIRM1 directs multiple crucial aspects of MN physiology, from their development to the acquisition of appropriate morphological features and motor function.

Produzione scientifica

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 - ()

11573/1692082 - 2023 - The long noncoding RNA nHOTAIRM1 is necessary for differentiation and activity of iPSC-derived spinal motor neurons
Tollis, P.; Vitiello, E.; Migliaccio, F.; D'ambra, E.; Rocchegiani, A.; Garone, M. G.; Bozzoni, I.; Rosa, A.; Carissimo, A.; Laneve, P.; Caffarelli, E. - 01a Articolo in rivista
rivista: CELL DEATH & DISEASE (Nature Group) pp. - - issn: 2041-4889 - wos: WOS:001101872900003 (2) - scopus: 2-s2.0-85176472807 (2)

11573/1619757 - 2021 - RNA deregulation in Amyotrophic Lateral Sclerosis: The noncoding perspective
Laneve, P.; Tollis, P.; Caffarelli, E. - 01g Articolo di rassegna (Review)
rivista: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (Basel (Matthaeustrasse 11) : Molecular Diversity Preservation International MDPI) pp. - - issn: 1661-6596 - wos: WOS:000707125800001 (18) - scopus: 2-s2.0-85115664432 (18)

11573/1429819 - 2020 - HOTAIRM1 regulates neuronal differentiation by modulating NEUROGENIN 2 and the downstream neurogenic cascade
Rea, Jessica; Menci, Valentina; Tollis, Paolo; Santini, Tiziana; Armaos, Alexandros; Garone, Maria Giovanna; Iberite, Federica; Cipriano, Andrea; Tartaglia, Gian Gaetano; Rosa, Alessandro; Ballarino, Monica; Laneve, Pietro; Caffarelli, Elisa - 01a Articolo in rivista
rivista: CELL DEATH & DISEASE (Nature Group) pp. - - issn: 2041-4889 - wos: WOS:000553100400002 (29) - scopus: 2-s2.0-85087954274 (27)

11573/1481384 - 2020 - HOTAIRM1 regulates neuronal differentiation by controlling NEUROGENIN 2 and the downstream neurogenic cascade
Rea, Jessica; Menci, Valentina; Tollis, Paolo; Santini, Tiziana; Tartaglia, Gian Gaetano; Rosa, Alessandro; Ballarino, Monica; Laneve, Pietro; Caffarelli, Elisa - 04f Poster
congresso: 25th Annual Meeting of the RNA Society (Online)
libro: 25th Annual Meeting of the RNA Society - ()

11573/1345007 - 2019 - HOTAIRM1 regulates neuronal differentiation by controlling NEUROGENIN 2 and the downstream neurogenic cascade
Rea, Jessica; Menci, Valentina; Tollis, Paolo; Santini, Tiziana; Alexandros, Armaos; Garone, Maria Giovanna; Iberite, Federica; Cipriano, Andrea; Tartaglia, Gian Gaetano; Rosa, Alessandro; Ballarino, Monica; Laneve, Pietro; Caffarelli, Elisa - 04f Poster
congresso: EMBO | EMBL Symposium: The Non-Coding Genome (EMBL Heidelberg, Germany)
libro: EMBO | EMBL Symposium: The Non-Coding Genome - ABSTRACT BOOK - ()

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