My research group has an established expertise in the study of post-transcriptional gene regulation in eukaryotes. In this regard, we are presently exploring the role of noncoding RNAs (microRNAs, long noncoding RNAs and circular RNAs) as regulative molecules in neuronal differentiation and studying their deregulation in neurological disorders, such as brain tumours (medulloblastoma and glioblastoma) and neurodegeneration (Amyotrophic Lateral Sclerosis-ALS). The main research projects, we are currently involved in, concern: 1) Identification and functional characterisation of novel long noncoding RNAs (lncRNAs) instructing neuronal differentiation programs and implicated in tumorigenesis (medulloblastoma and glioblastoma).
2) Characterisation of the noncoding transcriptome (including microRNAs, long noncoding RNAs and circular RNAs) in a FUS-ALS model, to decipher how the noncoding RNAs contribute to the ALS pathology and if their action can be reversed.
3) Functional characterisation of endoribonucleases involved in coding and non-coding RNA metabolism. We discovered the founding member of the Eukaryotic EndoU ribonuclease family, whose components are flexibly involved in important biological processes, such as ribosome biogenesis, tumorigenesis and viral replication. Upon characterization of the amphibian and human homologs, we are focusing on the Drosophila enzyme that we revealed to be essential for nervous system activity and to act as a positive regulator of the neurodegeneration-associated protein dTDP-43. We are analysing, by transcriptome analysis, the in vivo target repertoire of this endoribonuclease (mRNAs, miRNAs, lncRNAs, circRNAs) to determine their involvement in nervous system.
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1. Biscarini S, Capauto D, Peruzzi G, Lu L, Colantoni A, Santini T, Shneider NA, Caffarelli E, LaneveP, Bozzoni I (2018) Characterization of the lncRNA transcriptome in mESC-derived motor neurons: implications for FUS-ALS. Stem Cell Res. doi: 10.1016/j.scr.2018.01.037. 2. Capauto D, Colantoni A, Lu L, Santini T, Peruzzi G, Biscarini S, Morlando M, Shneider NA, Caffarelli E, Laneve P, Bozzoni I (2018) A regulatory circuitry between Gria2, miR-409, and miR-495 is affected by ALS FUS mutation in ESC-derived motor neurons. Mol Neurobiol doi: 10.1007/s12035-018-0884-4. 4. Laneve P, Po A, Favia A, Legnini I, Alfano V, Rea J, Di Carlo V, Bevilacqua V, Miele E, Mastronuzzi A, Carai A, Locatelli F, Bozzoni I, Ferretti E, Caffarelli E (2017) The long noncoding RNA linc-NeD125 controls the expression of medulloblastoma driver genes by microRNA sponge activity. Oncotarget 8(19):31003-31015; doi: 10.18632/oncotarget.16049. 5. Laneve P, Piacentini L, Casale AM, Capauto D, Gioia U, Cappucci U, Di Carlo V, Bozzoni I, Di Micco P, Morea V, Di Franco CA, Caffarelli E (2017) Drosophila CG3303 is an essential endoribonuclease linked to TDP-43-mediated neurodegeneration. Sci. Rep. 7, 41559; doi: 10.1038/srep41559 . 6. Bevilacqua V, Gioia U, Di Carlo V, Tortorelli AF, Colombo T, Bozzoni I, Laneve P, Caffarelli E (2015) Identification of linc-NeD125, a novel long non coding RNA that hosts miR-125b-1 and negatively controls proliferation of human neuroblastoma cells. RNA Biology 12(12):1323-37. 7. Gioia U, Di Carlo V, Caramanica P, Toselli C, Cinquino A, Marchioni M, Laneve P, Biagioni S, Bozzoni I, Cacci E, Caffarelli E (2014) miR-23a and miR-125b regulate neural stem/progenitor cell proliferation by targeting Musashi1. RNA Biology 11(9): 1105-12. 8. Di Carlo V, Grossi E, Laneve P, Morlando M, Dini Modigliani S, Ballarino M, Bozzoni I, Caffarelli E. (2013) TDP-43 regulates the Microprocessor complex activity during in vitro neuronal differentiation. Mol Neurobiol 48(3): 952-963. 9. Morlando M, Dini Modigliani S, Torrelli G, Rosa A, Di Carlo V, Caffarelli E and I Bozzoni (2012) FUS stimulates microRNA biogenesis by facilitating co-transcriptional Drosha recruitment. EMBO J 31 (24): 4502-4510. 10. Annibali D, Gioia U, Savino M, Laneve P, Caffarelli E, Nasi S (2012) A new module in neural differentiation control: two microRNAs upregulated by retinoic acid, miR-9 and -103, target the differentiation inhibitor ID2. PLoS One 7(7):e40269. Epub 2012 Jul 25. 11. Ragno R, Gioia U, Laneve P, Bozzoni I, Mai A, Caffarelli E. (2011) Identification of small-molecule inhibitors of the XendoU endoribonucleases family. ChemMedChem 6(10):1797-805. 12. E Caffarelli, P Filetici (2011) Epigenetic regulation in cancer development. Front Biosci 17: 2682-2694. 13. Laneve P, Gioia U, Andriotto A, Moretti F, Bozzoni I, Caffarelli E (2010) A minicircuitry involving REST and CREB controls miR-9-2 expression during human neuronal differentiation. Nucleic Acids Res 38(20):6895-905. 14. Ferretti E, De Smaele E, Po A, Di Marcotullio L, Tosi E, Espinola MSB, Di Rocco C, Riccardi R, Giangaspero F, Farcomeni A, Nofroni I, Laneve P, Gioia U, Caffarelli E, Bozzoni I., Screpanti I and Gulino A (2009) MicroRNA profiling in human medulloblastoma. Int J Cancer 24: 568-577 15. Laneve P, Gioia U, Ragno R, Altieri F, Di Franco C, Santini T, Arceci M, Bozzoni I, Caffarelli E (2008) The tumor marker human placental protein 11 is an endoribonuclease. J Biol Chem 283: 34712-34719 16. Ferretti E, De Smaele E, Miele E, Laneve P, Po A, Pelloni M, Paganelli A, Di Marcotullio L, Caffarelli E, Screpanti I, Bozzoni I, Gulino A (2008) Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. EMBO J 27: 2616-2627 17. Laneve P, Di Marcotullio L, Gioia U, Fiori ME, Ferretti E, Gulino A, Bozzoni I, Caffarelli E (2007) The interplay between microRNAs and the neurotrophin receptor tropomyosin-related kinase C controls proliferation of human neuroblastoma cells. Proc Natl Acad Sci USA 104: 7957-796 18. Renzi F, Caffarelli E, Laneve P, Bozzoni I, Brunori M, Vallone B (2006) The structure of the endoribonuclease XendoU: from small nucleolar RNA processing to severe acute respiratory syndrome coronavirus replication. Proc Natl Acad Sci USA 103 (33): 12365-12370 19. Renzi F, Panetta G, Vallone B, Brunori M, Arceci M, Bozzoni I, Laneve P, Caffarelli E (2006) Large-scale purification and crystallization of the endoribonuclease XendoU: troubleshooting with His-tagged proteins. Acta Cryst section F 62: 298-301 20. Fatica A, Rosa A, Fazi F, Ballarino M, Morlando M, De Angelis FG, Caffarelli E, Nervi C, Bozzoni I (2006) MicroRNAs and hematopoietic differentiation. Cold Spring Harb Symp Quant Biol 71:205-10. Review. 21. Gioia U, Laneve P, Dlakic M, Arceci M, Bozzoni I, Caffarelli E (2005) Functional characterization of XendoU, the endoribonuclease involved in small nucleolar RNA biosynthesis. J Biol Chem 280 (19): 18996-19002 |
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Within IBPM
Barbara Illi, Laboratorio Acidi Nucleici
IBPM Associate members
Irene Bozzoni, Dept. of Biology and Biotechnology C.Darwin, Sapienza University of Rome
With other Institutions
Elisabetta Ferretti, Dept. of Experimental Medicine, Sapienza University of Rome
Stefano Biagioni, Dept. of Biology and Biotechnology C.Darwin, Sapienza University of Rome
Lucia Piacentini, Dept. of Biology and Biotechnology C.Darwin, Sapienza University of Rome
Manuela Helmer Citterich, Dept. of Biology, Tor Vergata University, Rome
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Education and Professional Experience Main research interests Projects as Principal Investigator 2011-2016: Project IIT/Sapienza Center for Life Nanoscience: Novel Nanotech-Based Approaches for the Study and Treatment of Amyotrophic Lateral Sclerosis (500.000 €, funded by Istituto Italiano di Tecnologia) 2005-2007: Project Ricerche a tema libero of CNR: Identificazione di molecole inibitrici dell'attività di XendoU, l'omologo cellulare di una proteina essenziale per la replicazione e trascrizione dei coronavirus (7.767 €, funded by CNR) 1997-2000: Progetto Finalizzato Biotecnologie of CNR: Utilizzazione di nuove funzioni dell’RNA per ottenere l’inibizione mirata dell’espressione genica: produzione di modificazioni covalenti sito-specifiche di RNA target mediante l’uso di “snoRNA antisenso” opportunamente modificati (56.295€, funded by CNR) |