Functional annotation of human long noncoding RNAs via molecular phenotyping
- Jordan A. Ramilowski1,2,47,
- Chi Wai Yip1,2,47,
- Saumya Agrawal1,2,
- Jen-Chien Chang1,2,
- Yari Ciani3,
- Ivan V. Kulakovskiy4,5,
- Mickaël Mendez6,
- Jasmine Li Ching Ooi2,
- John F. Ouyang7,
- Nick Parkinson8,
- Andreas Petri9,
- Leonie Roos10,11,
- Jessica Severin1,2,
- Kayoko Yasuzawa1,2,
- Imad Abugessaisa1,2,
- Altuna Akalin12,
- Ivan V. Antonov13,
- Erik Arner1,2,
- Alessandro Bonetti2,
- Hidemasa Bono14,
- Beatrice Borsari15,
- Frank Brombacher16,17,
- Christopher J.F. Cameron18,23,46,
- Carlo Vittorio Cannistraci19,20,
- Ryan Cardenas21,
- Melissa Cardon1,
- Howard Chang22,
- Josée Dostie23,
- Luca Ducoli24,
- Alexander Favorov25,26,
- Alexandre Fort2,
- Diego Garrido15,
- Noa Gil27,
- Juliette Gimenez28,
- Reto Guler16,17,
- Lusy Handoko2,
- Jayson Harshbarger2,
- Akira Hasegawa1,2,
- Yuki Hasegawa2,
- Kosuke Hashimoto1,2,
- Norihito Hayatsu1,
- Peter Heutink29,
- Tetsuro Hirose30,
- Eddie L. Imada26,
- Masayoshi Itoh2,31,
- Bogumil Kaczkowski1,2,
- Aditi Kanhere21,
- Emily Kawabata2,
- Hideya Kawaji31,
- Tsugumi Kawashima1,2,
- S. Thomas Kelly1,
- Miki Kojima1,2,
- Naoto Kondo2,
- Haruhiko Koseki1,
- Tsukasa Kouno1,2,
- Anton Kratz2,
- Mariola Kurowska-Stolarska32,
- Andrew Tae Jun Kwon1,2,
- Jeffrey Leek26,
- Andreas Lennartsson33,
- Marina Lizio1,2,
- Fernando López-Redondo1,2,
- Joachim Luginbühl1,2,
- Shiori Maeda1,
- Vsevolod J. Makeev25,34,
- Luigi Marchionni26,
- Yulia A. Medvedeva13,34,
- Aki Minoda1,2,
- Ferenc Müller21,
- Manuel Muñoz-Aguirre15,
- Mitsuyoshi Murata1,2,
- Hiromi Nishiyori1,2,
- Kazuhiro R. Nitta1,2,
- Shuhei Noguchi1,2,
- Yukihiko Noro2,
- Ramil Nurtdinov15,
- Yasushi Okazaki1,2,
- Valerio Orlando35,
- Denis Paquette23,
- Callum J.C. Parr1,
- Owen J.L. Rackham7,
- Patrizia Rizzu29,
- Diego Fernando Sánchez Martinez26,
- Albin Sandelin36,
- Pillay Sanjana21,
- Colin A.M. Semple37,
- Youtaro Shibayama1,2,
- Divya M. Sivaraman1,2,
- Takahiro Suzuki1,2,
- Suzannah C. Szumowski2,
- Michihira Tagami1,2,
- Martin S. Taylor37,
- Chikashi Terao1,
- Malte Thodberg36,
- Supat Thongjuea2,
- Vidisha Tripathi38,
- Igor Ulitsky27,
- Roberto Verardo3,
- Ilya E. Vorontsov25,
- Chinatsu Yamamoto2,
- Robert S. Young39,
- J. Kenneth Baillie8,
- Alistair R.R. Forrest1,2,40,
- Roderic Guigó15,41,
- Michael M. Hoffman42,
- Chung Chau Hon1,2,
- Takeya Kasukawa1,2,
- Sakari Kauppinen9,
- Juha Kere33,43,
- Boris Lenhard10,11,44,
- Claudio Schneider3,45,
- Harukazu Suzuki1,2,
- Ken Yagi1,2,
- Michiel J.L. de Hoon1,2,
- Jay W. Shin1,2 and
- Piero Carninci1,2
- 1RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa 230-0045, Japan;
- 2RIKEN Center for Life Science Technologies, Yokohama, Kanagawa 230-0045, Japan;
- 3Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie (CIB), Trieste 34127, Italy;
- 4Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia;
- 5Institute of Protein Research, Russian Academy of Sciences, Pushchino 142290, Russia;
- 6Department of Computer Science, University of Toronto, Toronto, Ontario M5S 1A1, Canada;
- 7Program in Cardiovascular and Metabolic Disorders, Duke-National University of Singapore Medical School, Singapore 169857, Singapore;
- 8Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, United Kingdom;
- 9Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen 9220, Denmark;
- 10Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London W12 0NN, United Kingdom;
- 11Computational Regulatory Genomics, MRC London Institute of Medical Sciences, London W12 0NN, United Kingdom;
- 12Berlin Institute for Medical Systems Biology, Max Delbrük Center for Molecular Medicine in the Helmholtz Association, Berlin 13125, Germany;
- 13Institute of Bioengineering, Research Center of Biotechnology, Russian Academy of Sciences, Moscow 117312, Russia;
- 14Graduate School of Integrated Sciences for Life, Hiroshima University, Higashi-Hiroshima City 739-0046, Japan;
- 15Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Catalonia 08003, Spain;
- 16International Centre for Genetic Engineering and Biotechnology (ICGEB), University of Cape Town, Cape Town 7925, South Africa;
- 17Institute of Infectious Diseases and Molecular Medicine (IDM), Department of Pathology, Division of Immunology and South African Medical Research Council (SAMRC) Immunology of Infectious Diseases, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa;
- 18School of Computer Science, McGill University, Montréal, Québec H3G 1Y6, Canada;
- 19Biomedical Cybernetics Group, Biotechnology Center (BIOTEC), Center for Molecular and Cellular Bioengineering (CMCB), Center for Systems Biology Dresden (CSBD), Cluster of Excellence Physics of Life (PoL), Department of Physics, Technische Universität Dresden, Dresden 01062, Germany;
- 20Center for Complex Network Intelligence (CCNI) at the Tsinghua Laboratory of Brain and Intelligence (THBI), Department of Bioengineering, Tsinghua University, Beijing 100084, China;
- 21Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom;
- 22Center for Personal Dynamic Regulome, Stanford University, Stanford, California 94305, USA;
- 23Department of Biochemistry, Rosalind and Morris Goodman Cancer Research Center, McGill University, Montréal, Québec H3G 1Y6, Canada;
- 24Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, Zurich 8093, Switzerland;
- 25Department of Computational Systems Biology, Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119991, Russia;
- 26Department of Oncology, Johns Hopkins University, Baltimore, Maryland 21287, USA;
- 27Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel;
- 28Epigenetics and Genome Reprogramming Laboratory, IRCCS Fondazione Santa Lucia, Rome 00179, Italy;
- 29Genome Biology of Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen 72076, Germany;
- 30Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Japan;
- 31RIKEN Preventive Medicine and Diagnosis Innovation Program (PMI), Saitama 351-0198, Japan;
- 32Institute of Infection, Immunity, and Inflammation, University of Glasgow, Glasgow, Scotland G12 8QQ, United Kingdom;
- 33Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge 14157, Sweden;
- 34Moscow Institute of Physics and Technology, Dolgoprudny 141701, Russia;
- 35Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia;
- 36Department of Biology and BRIC, University of Copenhagen, Denmark, Copenhagen N DK2200, Denmark;
- 37MRC Human Genetics Unit, University of Edinburgh, Edinburgh EH4 2XU, United Kingdom;
- 38National Centre for Cell Science, Pune, Maharashtra 411007, India;
- 39Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh EH8 9AG, United Kingdom;
- 40Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, The University of Western Australia, Nedlands, Perth, Western Australia 6009, Australia;
- 41Universitat Pompeu Fabra (UPF), Barcelona, Catalonia 08002, Spain;
- 42Princess Margaret Cancer Centre, Toronto, Ontario M5G 1L7, Canada;
- 43Stem Cells and Metabolism Research Program, University of Helsinki and Folkhälsan Research Center, 00290 Helsinki, Finland;
- 44Sars International Centre for Marine Molecular Biology, University of Bergen, Bergen N-5008, Norway;
- 45Department of Medicine and Consorzio Interuniversitario Biotecnologie p.zle Kolbe 1 University of Udine, Udine 33100, Italy;
- 46Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06510, USA
-
↵47 These authors contributed equally to this work.
Abstract
Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.254219.119.
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Freely available online through the Genome Research Open Access option.
- Received July 12, 2019.
- Accepted June 24, 2020.
This article, published in Genome Research, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
