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).
lncRNAs, that include also circular RNAs, are very versatile transcripts that may regulate gene expression at multiple levels, from epigenetic to transcriptional and post-transcriptional ones. We are particularly interested in determining which non-coding RNAs are important for early and late differentiation events and in understanding how these RNAs control gene expression, which are their target genes and their mechanism of action. This ultimately allow us to build RNA-based regulatory circuitries relevant for normal neuronal physiology and possibly deranged in neurological tumours.

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.  
The protein FUS widely controls RNA metabolism making ALS an RNA disorder: for our aim, we use in vitro-derived mouse motor neurons (MNs), the neuronal subtype primarily affected in ALS, carrying one of the most severe ALS-associated FUS mutations. We found specific classes of microRNAs, long noncoding RNAs and circular RNAs, which are specifically affected by the mutated version of FUS, both in terms of biogenesis and/or expression, highlighting a role for these transcripts in ALS. 

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.

 These projects are supported in the framework of Project on Life Nanoscience of Italian Institute of Technology (IIT)  and Progetto Bandiera Epigenomica (Epigen)

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. 
3. Errichelli L, Dini Modigliani S, Laneve P, Colantoni A, Legnini I, Capauto D, Rosa A, De Santis R, Scarfo’ R, Peruzzi G, Lu L, Caffarelli E, Shneider N, Morlando M, Bozzoni I (2017) FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons. Nat Commun. 8:14741. doi: 10.1038/ncomms14741.

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

Pietro Laneve           IBPM Researcher
Massimo Arceci         IBPM Technician 
Jessica Rea               PhD student
Valentina Menci         Master degree student
Paolo Tollis                Master degree student

Education and Professional Experience
- 2001 to date: Senior Researcher of CNR,  Institute of Molecular Biology and Pathology - Rome
- 1988-2001 : Researcher of CNR, Centre of Nucleic Acids -Rome
- 1989-1990: Associate Researcher, Yale University - School of Medicine (USA)
- 1984-1988: Associate Researcher of CNR, Centre of Nucleic Acids - Rome
- 1986 : Visiting scientist at the University of Heidelberg, Germany (one month, lab Prof. Keller)
- 1984 : EMBO fellow, Eidgenössische Technische Hochschule, Zurich (Switzerland)
- 1982-1984: trainee at Centre of Nucleic Acids of CNR - Rome 
- 1982 : Degree (110/110 cum laude) in Biological Sciences-Sapienza University of Rome

 
Academic commitments 
-Academic Lecturer at Sapienza University of Rome - course "Epigenetic control in cell differentiation" for Laurea Magistrale in Biologia e Tecnologie Cellulari (since 2012-2013 academic year)
- Lecturer as invited speaker in high formation courses (PhD courses, Erasmus courses)
- Member of  PhD Committee in Genetics and Molecular Biology (since February 2015)
- Member of the Editorial Board of International Scholarly Research Notices-Molecular Biology subject area and referee for several international journals
- Member of the Scientific Committee of the journal “Il giornale del linguaggio universale: DNA e…”
- Group leader of a research group at IBPM, at Dept. of Biology and Biotechnology, Sapienza  University
- Supervisor of first level and PhD theses in Genetics and Molecular Biology
- Author of 46 papers on highly qualified international journals and holder of 1 patent extended to U.S.
- Member of the Italian Society of Biophysics and Molecular Biology
- Elected member of the IBPM Committee – CNR (2009-2015)

 Main research interests
- Gene expression regulation at the post-transcriptional level
- Biogenesis and function of non-coding RNAs (small nucleolar RNAs, microRNAs, long non-coding   RNAs)
- Role of non-coding RNAs in neuronal differentiation and pathology (tumours and neurodegeneration)
- Structural and functional characterisation of endoribonucleases involved in RNA metabolism

Projects as Principal Investigator
2016-2018: The Epigenomics Flagship Project EPIGEN: Role of long non-coding RNA in cell differentiation and disease (60.000 €, funded by MIUR and CNR)

2013-2015: The Epigenomics Flagship Project EPIGEN: Role of long non-coding RNA in cell differentiation and disease (29.100 €, funded by MIUR and CNR)

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)