Our laboratory explores the function of long non-coding RNAs (lncRNAs) 11human genome while developing original transcriptome technologies.and the regulatory elements including promoters and enhancers in the To understand transcriptome regulation, we organized the FANTOM6 Phase II project, involving ~390 researchers from more than 70 institutes in 20 countries. Previously, we revealed that more than half of lncRNAs in the cell localize in the nucleus and the majority of them are in the chromatin-bound fraction. The phase II project aims at elucidating the function of chromatin-bound RNAs using interactome data generated with our RADICL-seq technol-ogy, which captures genome-wide RNA-DNA interactions in the nucleus, from more than 15 cell types, establishing novel paradigms on RNAs interacting with and regulating chromatin. To deepen discussions, we organized the FANTOM6 on-site meetings in Milan on April 12-14 and October 2-3, 2023.Including FANTOM, many international efforts have produced gene an-notation databases. In a review published this year (Amaral et al., Nature) we discussed the need for universal annotation standards and new technologies to complete the human transcript catalog for its use in the medical field.We also study the structure-function relationship of lncRNAs using SINE-UPs, antisense lncRNAs that enhance the translation of targeted protein-coding mRNAs. By using in-cell secondary structure probing, we demonstrated that SINE-derived RNAs embedded in the SINEUPs: 1) contain structurally con-served short structure motifs essential for translation enhancement; 2) change structure between the nucleus and cytoplasm, associating with compartment-specific binding to RNA binding proteins (RBPs); 3) directly interact with rRNAs. In general, functional domains of lncRNAs show little conservation, limited to short sequences that, however, fold into similar structures essential for the function of SINEUPs, providing binding sites for RBPs and rRNAs even in evolutionarily distant SINE-transcribed RNAs (Sharma et all, Nat Comm, in press).Figure: FANTOM6 Phase 2 Spring MeetingFANTOM6 Phase 2 Spring Meeting was held on April 12-14, 2023, at the Human Technopole in Milan, Italy.Recent Major PublicationsAmaral P, Carbonell-Sala S, De La Vega FM, Faial T, Frank-ish A, Gingeras T, Guigo R, Harrow JL, Hatzigeorgiou AG, Johnson R, Murphy TD, Pertea M, Pruitt KD, Pujar S, Takahashi H, Ulitsky I, Varabyou A, Wells CA, Yandell M, Carninci P, Salzberg SL. The status of the human gene catalogue. Nature 622, 41-47 (2023)Robbe P, Ridout KE, Vavoulis DV, Dréau H, Kinnersley B, Denny N, Chubb D, Appleby N, Cutts A, Cornish AJ, Lopez-Pascua L, Clifford R, Burns A, Stamatopoulos B, Cabes M, Alsolami R, Antoniou P, Oates M, Cavalieri D, Genomics England Research Consortium, CLL pilot consortium, Gibson J, Prabhu AV, Schwessinger R, Jen-nings D, James T, Maheswari U, Duran-Ferrer M, Carninci P, Knight SJL, Månsson R, Hughes J, Davies J, Ross M, Bentley D, Strefford JC, Devereux S, Pettitt AR, Hillmen P, Caulfield MJ, Houlston RS, Martín-Subero JI, Schuh A. Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features. Nat Genet 54, 1675-1689 (2022)Pascarella G, Hon CC, Hashimoto K, Busch A, Luginbühl J, Parr C, Yip WH, Abe K, Kratz A, Bonetti A, Agostini F, Severin J, Murayama S, Suzuki Y, Gustincich S, Frith M, Carninci P. Recombination of repeat elements generates somatic complexity in human genomes. Cell 185, 3025-3040.e6 (2022)Invited presentationsCarninci P. “Genomics regulation and long non-coding RNAs functions” Special Lecture Tokuron & Tokupro FY2023 CIBoG/AI-MAILs Omics Analysis Program at the Nagoya University (Aichi, Japan/Online) November 2023Carninci P. “Inferring function of lncRNAs through in-teractome with chromatin” Human Genetics Asia 2023 (Tokyo, Japan) October 2023Carninci P. “Genomics regulation by long non-coding RNAs” Distinguished Visitor Lecture Series-EMBL Rome, (Rome, Italy) June 2023Carninci P. “Global Analysis of Transcriptome and its Interaction with Chromatin in the FANTOM6 Project” Gordon Research Conference, Cancer Genetics and Epigenetics, Precision Cancer Medicine for the Evolving Cancer Genome and Epigenome (Lucca, Italy) May 2023Carninci P. “Long non-coding RNAs in cellular networks and genome regulation” Interdisciplinary Science Con-ference in Okinawa (ISCO 2023) -Physics and Mathemat-ics meet Medical Science- (Okinawa, Japan) March 2023Laboratory for Transcriptome TechnologyTeam Leader: Piero Carninci
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