Functional annotation of human long noncoding RNAs via molecular phenotyping.

Jordan A Ramilowski, Chi Wai Yip, Saumya Agrawal, Jen-Chien Chang, Yari Ciani, Ivan V Kulakovskiy, Mickaël Mendez, Jasmine Li Ching Ooi, John F Ouyang, Nick Parkinson, Andreas Petri, Leonie Roos, Jessica Severin, Kayoko Yasuzawa, Imad Abugessaisa, Altuna Akalin, Ivan V Antonov, Erik Arner, Alessandro Bonetti, Hidemasa BonoBeatrice Borsari, Frank Brombacher, Chris J F Cameron, Carlo Vittorio Cannistraci, Ryan Cardenas, Melissa Cardon, Howard Chang, Josée Dostie, Luca Ducoli, Alexander Favorov, Alexandre Fort, Diego Garrido, Noa Gil, Juliette Gimenez, Reto Guler, Lusy Handoko, Jayson Harshbarger, Akira Hasegawa, Yuki Hasegawa, Kosuke Hashimoto, Norihito Hayatsu, Peter Heutink, Tetsuro Hirose, Eddie L Imada, Masayoshi Itoh, Bogumil Kaczkowski, Aditi Kanhere, Emily Kawabata, Hideya Kawaji, Tsugumi Kawashima, S Thomas Kelly, Miki Kojima, Naoto Kondo, Haruhiko Koseki, Tsukasa Kouno, Anton Kratz, Mariola Kurowska-Stolarska, Andrew Tae Jun Kwon, Jeffrey Leek, Andreas Lennartsson, Marina Lizio, Fernando López-Redondo, Joachim Luginbühl, Shiori Maeda, Vsevolod J Makeev, Luigi Marchionni, Yulia A Medvedeva, Aki Minoda, Ferenc Müller, Manuel Muñoz-Aguirre, Mitsuyoshi Murata, Hiromi Nishiyori, Kazuhiro R Nitta, Shuhei Noguchi, Yukihiko Noro, Ramil Nurtdinov, Yasushi Okazaki, Valerio Orlando, Denis Paquette, Callum J C Parr, Owen J L Rackham, Patrizia Rizzu, Diego Fernando Sánchez Martinez, Albin Sandelin, Pillay Sanjana, Colin A M Semple, Youtaro Shibayama, Divya M Sivaraman, Takahiro Suzuki, Suzannah C Szumowski, Michihira Tagami, Martin S Taylor, Chikashi Terao, Malte Thodberg, Supat Thongjuea, Vidisha Tripathi, Igor Ulitsky, Roberto Verardo, Ilya E Vorontsov, Chinatsu Yamamoto, Robert S Young, J Kenneth Baillie, Alistair R R Forrest, Roderic Guigó, Michael M Hoffman, Chung Chau Hon, Takeya Kasukawa, Sakari Kauppinen, Juha Kere, Boris Lenhard, Claudio Schneider, Harukazu Suzuki, Ken Yagi, Michiel J L de Hoon, Jay W Shin, Piero Carninci

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83 Scopus citations

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.
Original languageEnglish (US)
JournalGenome research
DOIs
StatePublished - Jul 29 2020

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We thank Linda Kostrencic, Hiroto Atsui, Emi Ito, Nobuyuki Takeda, Tsutomu Saito, Teruaki Kitakura, Yumi Hara, Machiko Kashiwagi, and Masaaki Furuno at RIKEN Yokohama for assistance in arranging collaboration agreements, ethics applications, computational infrastructure, and the FANTOM6 meetings. We also thank RIKEN GeNAS for generation and sequencing of the CAGE libraries and subsequent data processing. FANTOM6 was made possible by a Research Grant for RIKEN Center for Life Science Technology, Division of Genomic Technologies (CLST DGT) and RIKEN Center for Integrative Medical Sciences (IMS) from MEXT, Japan. I.V.K. and I.E.V. were supported by Russian Foundation for Basic Research (RFBR) 18-34-20024, B.B. is supported by the fellowship 2017FI_B00722 from the Secretaria d'Universitats i Recerca del Departament d'Empresa i Coneixement (Generalitat de Catalunya) and the European Social Fund (ESF), A. Favorov was supported by National Institutes of Health (NIH) P30 CA006973 and RFBR 17-00-00208, D.G. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship (LCF/BQ/SO15/52260001), E.L.I. and L.M. were supported by NIH National Cancer Institute Grant R01CA200859 and Department of Defense (DOD) award W81XWH-16-1-0739, M.K.-S. was supported by Versus Arthritis UK 20298, A.L. was supported by the Swedish Cancer Society, The Swedish Research Council, the Swedish Childhood Cancer fund, Radiumhemmets forsknigsfonder; V.J.M. was supported by the Russian Academy of Sciences Project 0112-2019-0001; Y.A.M. was supported by Russian Science Foundation (RSF) grant 18-14-00240, A.S. was supported by Novo Nordisk Foundation, Lundbeck Foundation, Danish Cancer Society, Carlsberg Foundation, Independent Research Fund Denmark, A.R.R.F. is currently supported by an Australian National Health and Medical Research Council Fellowship APP1154524, M.M.H. was supported by Natural Sciences and Engineering Research Council of Canada (RGPIN-2015-3948), C.S. was supported by the Interuniversity Consortium for Biotechnology (CIB) from the Italian Ministry of Education, University and Research (MIUR) grant n.974,CMPT177780. J. Luginbühl was supported by Japan Society for the Promotion of Science (JSPS) Postdoctoral Fellowship for Foreign Researchers. C.J.C.P. was supported by RIKEN Special Post-Doctoral Research (SPDR) fellowship.

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