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Functional Annotation of Human Long Non-Coding RNAs via Molecular Phenotyping

By Jordan Ramilowski, Chi Wai Yip, Saumya Agrawal, Jen-Chien Chang, Yari Ciani, Ivan V. Kulakovskiy, Mickael Mendez, Jasmine Li Ching Ooi, John F. Ouyang, Nick Parkinson, Andreas Petri, Leonie Roos, Jessica Severin, Kayoko Yasuzawa, Imad Abugessaisa, Altuna Akalin, Ivan Antonov, Erik Arner, Alessandro Bonetti, Hidemasa Bono, Beatrice Borsari, Frank Brombacher, Carlo Vittorio Cannistraci, Christopher J.F. Cameron, Ryan Cardenas, Melissa Cardon, Howard Chang, Josée Dostie, Luca Ducoli, Alexander V 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, Tom 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 Lopez, Joachim Luginbühl, Shiori Maeda, Vsevolod Makeev, Luigi Marchionni, Yulia A. Medvedeva, Aki Minoda, Ferenc Müller, Manuel Munoz Aguirre, Mitsuyoshi Murata, Hiromi Nishiyori, Kazuhiro Nitta, Shuhei Noguchi, Yukihiko Noro, Ramil Nurtdinov, Yasushi Okazaki, Valerio Orlando, Denis Paquette, Callum Parr, Owen J. L. Rackham, Patrizia Rizzu, Diego Fernando Sanchez, Albin Sandelin, Pillay Sanjana, Colin A.M. Semple, Harshita Sharma, Youtaro Shibayama, Divya Sivaraman, Takahiro Suzuki, Suzannah Szumowski, Michihira Tagami, Martin S. Taylor, Chikashi Terao, Malte Thodberg, Supat Thongjuea, Vidisha Tripathi, Igor Ulitsky, Roberto Verardo, Ilya 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, FANTOM consortium, Michiel de Hoon, Jay W Shin, Piero Carninci

Posted 14 Jul 2019
bioRxiv DOI: 10.1101/700864

Long non-coding RNAs (lncRNAs) constitute the majority of transcripts in mammalian genomes and yet, their functions remain largely unknown. We systematically suppressed 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). The resulting transcriptomic profiles recapitulated the observed cellular phenotypes, yielding specific roles for over 40% of analyzed lncRNAs in regulating distinct biological pathways, transcriptional machinery, alternative promoter activity and architecture usage. Overall, combining cellular and molecular profiling provided a powerful approach to unravel the distinct functions of lncRNAs, which we highlight with specific functional roles for ZNF213-AS1 and lnc-KHDC3L-2.

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