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; Mickael 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 Bono; Beatrice Borsari; Frank Brombacher; Chris J. F. Cameron; Carlo Vittorio Cannistraci; Ryan Cardenas; Melissa Cardon; Howard Chang; Josee 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 Lopez-Redondo; Joachim Luginbuhl; Shiori Maeda; Vsevolod J. Makeev; Luigi Marchionni; Yulia A. Medvedeva; Aki Minoda; Ferenc Mueller; Manuel Munoz-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 Sanchez 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 Guigo; 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

doi:10.1101/gr.254219.119

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, Mickael 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, Josee 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 Lopez-Redondo, Joachim Luginbuhl, Shiori Maeda, Vsevolod J. Makeev, Luigi Marchionni, Yulia A. Medvedeva, Aki Minoda, Ferenc Mueller, Manuel Munoz-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 Sanchez 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 Guigo, 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

Department of Immunology and Regenerative Biology

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

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-todate 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.

Errata: The authors would like to correct Figure 3, panel J, in which the rightmost upper image of SA-β-gal stained 293T cells following short hairpin RNA (shRNA)-mediated knockdown of RRAS2 with sh769 (RRAS2-KD-sh769) was inadvertently, and due to a labeling error, taken from the same original source image presented in the middle upper panel, which shows increased SA-β-gal activity following RRAS2 knockdown by a different shRNA (sh646). This correction does not affect any of the conclusions of the article. The corrected image representative of RRAS2-KD-sh769 is provided below, and Figure 3 has been updated in the article online.

Original language	English
Pages (from-to)	1060-1072
Number of pages	13
Journal	Genome Research
Volume	30
Issue number	7
DOIs	https://doi.org/10.1101/gr.254219.119
State	Published - Jul 2020

All Science Journal Classification (ASJC) codes

Genetics
Genetics(clinical)

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10.1101/gr.254219.119License: CC BY-NC

Cite this

Ramilowski, J. A., Yip, C. W., Agrawal, S., Chang, J.-C., Ciani, Y., Kulakovskiy, I. V., Mendez, M., Ooi, J. L. C., Ouyang, J. F., Parkinson, N., Petri, A., Roos, L., Severin, J., Yasuzawa, K., Abugessaisa, I., Akalin, A., Antonov, I. V., Arner, E., Bonetti, A., ... Carninci, P. (2020). Functional annotation of human long noncoding RNAs via molecular phenotyping. Genome Research, 30(7), 1060-1072. https://doi.org/10.1101/gr.254219.119

@article{3bc25657ba5b4245a57a2c34a322ca72,

title = "Functional annotation of human long noncoding RNAs via molecular phenotyping",

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-todate 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.Errata: The authors would like to correct Figure 3, panel J, in which the rightmost upper image of SA-β-gal stained 293T cells following short hairpin RNA (shRNA)-mediated knockdown of RRAS2 with sh769 (RRAS2-KD-sh769) was inadvertently, and due to a labeling error, taken from the same original source image presented in the middle upper panel, which shows increased SA-β-gal activity following RRAS2 knockdown by a different shRNA (sh646). This correction does not affect any of the conclusions of the article. The corrected image representative of RRAS2-KD-sh769 is provided below, and Figure 3 has been updated in the article online.",

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

note = "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. Luginb{\"u}hl 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.",

year = "2020",

month = jul,

doi = "10.1101/gr.254219.119",

language = "الإنجليزيّة",

volume = "30",

pages = "1060--1072",

journal = "Genome Research",

issn = "1088-9051",

publisher = "Cold Spring Harbor Laboratory Press",

number = "7",

}

Ramilowski, JA, Yip, CW, Agrawal, S, Chang, J-C, Ciani, Y, Kulakovskiy, IV, Mendez, M, Ooi, JLC, Ouyang, JF, Parkinson, N, Petri, A, Roos, L, Severin, J, Yasuzawa, K, Abugessaisa, I, Akalin, A, Antonov, IV, Arner, E, Bonetti, A, Bono, H, Borsari, B, Brombacher, F, Cameron, CJF, Cannistraci, CV, Cardenas, R, Cardon, M, Chang, H, Dostie, J, Ducoli, L, Favorov, A, Fort, A, Garrido, D, Gil, N, Gimenez, J, Guler, R, Handoko, L, Harshbarger, J, Hasegawa, A, Hasegawa, Y, Hashimoto, K, Hayatsu, N, Heutink, P, Hirose, T, Imada, EL, Itoh, M, Kaczkowski, B, Kanhere, A, Kawabata, E, Kawaji, H, Kawashima, T, Kelly, ST, Kojima, M, Kondo, N, Koseki, H, Kouno, T, Kratz, A, Kurowska-Stolarska, M, Kwon, ATJ, Leek, J, Lennartsson, A, Lizio, M, Lopez-Redondo, F, Luginbuhl, J, Maeda, S, Makeev, VJ, Marchionni, L, Medvedeva, YA, Minoda, A, Mueller, F, Munoz-Aguirre, M, Murata, M, Nishiyori, H, Nitta, KR, Noguchi, S, Noro, Y, Nurtdinov, R, Okazaki, Y, Orlando, V, Paquette, D, Parr, CJC, Rackham, OJL, Rizzu, P, Martinez, DFS, Sandelin, A, Sanjana, P, Semple, CAM, Shibayama, Y, Sivaraman, DM, Suzuki, T, Szumowski, SC, Tagami, M, Taylor, MS, Terao, C, Thodberg, M, Thongjuea, S, Tripathi, V, Ulitsky, I, Verardo, R, Vorontsov, IE, Yamamoto, C, Young, RS, Baillie, JK, Forrest, ARR, Guigo, R, Hoffman, MM, Hon, CC, Kasukawa, T, Kauppinen, S, Kere, J, Lenhard, B, Schneider, C, Suzuki, H, Yagi, K, Hoon, MJLD, Shin, JW & Carninci, P 2020, 'Functional annotation of human long noncoding RNAs via molecular phenotyping', Genome Research, vol. 30, no. 7, pp. 1060-1072. https://doi.org/10.1101/gr.254219.119

TY - JOUR

T1 - Functional annotation of human long noncoding RNAs via molecular phenotyping

AU - Ramilowski, Jordan A.

AU - Yip, Chi Wai

AU - Agrawal, Saumya

AU - Chang, Jen-Chien

AU - Ciani, Yari

AU - Kulakovskiy, Ivan V.

AU - Mendez, Mickael

AU - Ooi, Jasmine Li Ching

AU - Ouyang, John F.

AU - Parkinson, Nick

AU - Petri, Andreas

AU - Roos, Leonie

AU - Severin, Jessica

AU - Yasuzawa, Kayoko

AU - Abugessaisa, Imad

AU - Akalin, Altuna

AU - Antonov, Ivan V.

AU - Arner, Erik

AU - Bonetti, Alessandro

AU - Bono, Hidemasa

AU - Borsari, Beatrice

AU - Brombacher, Frank

AU - Cameron, Chris J. F.

AU - Cannistraci, Carlo Vittorio

AU - Cardenas, Ryan

AU - Cardon, Melissa

AU - Chang, Howard

AU - Dostie, Josee

AU - Ducoli, Luca

AU - Favorov, Alexander

AU - Fort, Alexandre

AU - Garrido, Diego

AU - Gil, Noa

AU - Gimenez, Juliette

AU - Guler, Reto

AU - Handoko, Lusy

AU - Harshbarger, Jayson

AU - Hasegawa, Akira

AU - Hasegawa, Yuki

AU - Hashimoto, Kosuke

AU - Hayatsu, Norihito

AU - Heutink, Peter

AU - Hirose, Tetsuro

AU - Imada, Eddie L.

AU - Itoh, Masayoshi

AU - Kaczkowski, Bogumil

AU - Kanhere, Aditi

AU - Kawabata, Emily

AU - Kawaji, Hideya

AU - Kawashima, Tsugumi

AU - Kelly, S. Thomas

AU - Kojima, Miki

AU - Kondo, Naoto

AU - Koseki, Haruhiko

AU - Kouno, Tsukasa

AU - Kratz, Anton

AU - Kurowska-Stolarska, Mariola

AU - Kwon, Andrew Tae Jun

AU - Leek, Jeffrey

AU - Lennartsson, Andreas

AU - Lizio, Marina

AU - Lopez-Redondo, Fernando

AU - Luginbuhl, Joachim

AU - Maeda, Shiori

AU - Makeev, Vsevolod J.

AU - Marchionni, Luigi

AU - Medvedeva, Yulia A.

AU - Minoda, Aki

AU - Mueller, Ferenc

AU - Munoz-Aguirre, Manuel

AU - Murata, Mitsuyoshi

AU - Nishiyori, Hiromi

AU - Nitta, Kazuhiro R.

AU - Noguchi, Shuhei

AU - Noro, Yukihiko

AU - Nurtdinov, Ramil

AU - Okazaki, Yasushi

AU - Orlando, Valerio

AU - Paquette, Denis

AU - Parr, Callum J. C.

AU - Rackham, Owen J. L.

AU - Rizzu, Patrizia

AU - Martinez, Diego Fernando Sanchez

AU - Sandelin, Albin

AU - Sanjana, Pillay

AU - Semple, Colin A. M.

AU - Shibayama, Youtaro

AU - Sivaraman, Divya M.

AU - Suzuki, Takahiro

AU - Szumowski, Suzannah C.

AU - Tagami, Michihira

AU - Taylor, Martin S.

AU - Terao, Chikashi

AU - Thodberg, Malte

AU - Thongjuea, Supat

AU - Tripathi, Vidisha

AU - Ulitsky, Igor

AU - Verardo, Roberto

AU - Vorontsov, Ilya E.

AU - Yamamoto, Chinatsu

AU - Young, Robert S.

AU - Baillie, J. Kenneth

AU - Forrest, Alistair R. R.

AU - Guigo, Roderic

AU - Hoffman, Michael M.

AU - Hon, Chung Chau

AU - Kasukawa, Takeya

AU - Kauppinen, Sakari

AU - Kere, Juha

AU - Lenhard, Boris

AU - Schneider, Claudio

AU - Suzuki, Harukazu

AU - Yagi, Ken

AU - Hoon, Michiel J. L. de

AU - Shin, Jay W.

AU - Carninci, Piero

N1 - 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.

PY - 2020/7

Y1 - 2020/7

N2 - 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-todate 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.Errata: The authors would like to correct Figure 3, panel J, in which the rightmost upper image of SA-β-gal stained 293T cells following short hairpin RNA (shRNA)-mediated knockdown of RRAS2 with sh769 (RRAS2-KD-sh769) was inadvertently, and due to a labeling error, taken from the same original source image presented in the middle upper panel, which shows increased SA-β-gal activity following RRAS2 knockdown by a different shRNA (sh646). This correction does not affect any of the conclusions of the article. The corrected image representative of RRAS2-KD-sh769 is provided below, and Figure 3 has been updated in the article online.

AB - 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-todate 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.Errata: The authors would like to correct Figure 3, panel J, in which the rightmost upper image of SA-β-gal stained 293T cells following short hairpin RNA (shRNA)-mediated knockdown of RRAS2 with sh769 (RRAS2-KD-sh769) was inadvertently, and due to a labeling error, taken from the same original source image presented in the middle upper panel, which shows increased SA-β-gal activity following RRAS2 knockdown by a different shRNA (sh646). This correction does not affect any of the conclusions of the article. The corrected image representative of RRAS2-KD-sh769 is provided below, and Figure 3 has been updated in the article online.

UR - http://www.scopus.com/inward/record.url?scp=85089203111&partnerID=8YFLogxK

U2 - 10.1101/gr.254219.119

DO - 10.1101/gr.254219.119

M3 - مقالة

SN - 1088-9051

VL - 30

SP - 1060

EP - 1072

JO - Genome Research

JF - Genome Research

IS - 7

ER -

Functional annotation of human long noncoding RNAs via molecular phenotyping

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