On the origin and evolution of RNA editing in metazoans
Pei Zhang,
Yuanzhen Zhu,
Qunfei Guo,
Ji Li,
Xiaoyu Zhan,
Hao Yu,
Nianxia Xie,
Huishuang Tan,
Nina Lundholm,
Lydia Garcia-Cuetos,
Michael D. Martin,
Meritxell Antó Subirats,
Yi-Hsien Su,
Iñaki Ruiz-Trillo,
Mark Q. Martindale,
Jr-Kai Yu,
M. Thomas P. Gilbert,
Guojie Zhang,
Qiye Li
Affiliations
Pei Zhang
BGI-Shenzhen, Shenzhen 518083, China; Section for Ecology and Evolution, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark
Yuanzhen Zhu
BGI Research-Wuhan, BGI, Wuhan 430074, China
Qunfei Guo
BGI-Shenzhen, Shenzhen 518083, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
Ji Li
BGI Research-Wuhan, BGI, Wuhan 430074, China
Xiaoyu Zhan
BGI-Shenzhen, Shenzhen 518083, China
Hao Yu
BGI-Shenzhen, Shenzhen 518083, China
Nianxia Xie
BGI-Shenzhen, Shenzhen 518083, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
Huishuang Tan
BGI-Shenzhen, Shenzhen 518083, China
Nina Lundholm
Natural History Museum of Denmark, University of Copenhagen, 1353 Copenhagen, Denmark
Lydia Garcia-Cuetos
Natural History Museum of Denmark, University of Copenhagen, 1353 Copenhagen, Denmark
Michael D. Martin
Department of Natural History, NTNU University Museum, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway; Center for Theoretical Evolutionary Genomics, Department of Integrative Biology, University of California Berkeley, Berkeley, CA 94720, USA
Meritxell Antó Subirats
Institute of Evolutionary Biology, UPF-CSIC Barcelona, 08003 Barcelona, Spain
Yi-Hsien Su
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan
Iñaki Ruiz-Trillo
Institute of Evolutionary Biology, UPF-CSIC Barcelona, 08003 Barcelona, Spain; ICREA, Passeig Lluís Companys 23, 08010 Barcelona, Catalonia, Spain; Departament de Genètica, Microbiologia i Estadística, Facultat de Bilogia, Universitat de Barcelona (UB), 08028 Barcelona, Spain
Mark Q. Martindale
The Whitney Laboratory for Marine Bioscience, University of Florida, St. Augustine, FL 32080, USA
Jr-Kai Yu
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 11529, Taiwan; Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, Yilan 26242, Taiwan
M. Thomas P. Gilbert
Department of Natural History, NTNU University Museum, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway; Center for Evolutionary Hologenomics, The GLOBE Institute, University of Copenhagen, 1353 Copenhagen, Denmark
Guojie Zhang
Center of Evolutionary and Organismal Biology, & Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, China; Liangzhu Laboratory, Zhejiang University Medical Center, 1369 West Wenyi Road, Hangzhou 311121, China; State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; Villum Centre for Biodiversity Genomics, Section for Ecology and Evolution, Department of Biology, University of Copenhagen, 2100 Copenhagen, Denmark; Corresponding author
Qiye Li
BGI-Shenzhen, Shenzhen 518083, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding author
Summary: Extensive adenosine-to-inosine (A-to-I) editing of nuclear-transcribed mRNAs is the hallmark of metazoan transcriptional regulation. Here, by profiling the RNA editomes of 22 species that cover major groups of Holozoa, we provide substantial evidence supporting A-to-I mRNA editing as a regulatory innovation originating in the last common ancestor of extant metazoans. This ancient biochemistry process is preserved in most extant metazoan phyla and primarily targets endogenous double-stranded RNA (dsRNA) formed by evolutionarily young repeats. We also find intermolecular pairing of sense-antisense transcripts as an important mechanism for forming dsRNA substrates for A-to-I editing in some but not all lineages. Likewise, recoding editing is rarely shared across lineages but preferentially targets genes involved in neural and cytoskeleton systems in bilaterians. We conclude that metazoan A-to-I editing might first emerge as a safeguard mechanism against repeat-derived dsRNA and was later co-opted into diverse biological processes due to its mutagenic nature.
