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Direct identification of A-to-I editing sites with nanopore native RNA sequencing.
Nguyen TA, Heng JWJ, Kaewsapsak P, Kok EPL, Stanojević D, Liu H, Cardilla A, Praditya A, Yi Z, Lin M, Aw JGA, Ho YY, Peh KLE, Wang Y, Zhong Q, Heraud-Farlow J, Xue S, Reversade B, Walkley C, Ho YS, Šikić M, Wan Y, Tan MH.
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Inosine is a prevalent RNA modification in animals and is formed when an adenosine is deaminated by the ADAR family of enzymes. Traditionally, inosines are identified indirectly as variants from Illumina RNA-sequencing data because they are interpreted as guanosines by cellular machineries. However, this indirect method performs poorly in protein-coding regions where exons are typically short, in non-model organisms with sparsely annotated single-nucleotide polymorphisms, or in disease contexts where unknown DNA mutations are pervasive. Here, we show that Oxford Nanopore direct RNA sequencing can be used to identify inosine-containing sites in native transcriptomes with high accuracy. We trained convolutional neural network models to distinguish inosine from adenosine and guanosine, and to estimate the modification rate at each editing site. Furthermore, we demonstrated their utility on the transcriptomes of human, mouse and Xenopus. Our approach expands the toolkit for studying adenosine-to-inosine editing and can be further extended to investigate other RNA modifications.
NMRC/OFIRG/0017/2016 MOH | National Medical Research Council (NMRC), Global Investigatorship European Molecular Biology Organization (EMBO), NRF2017-NRF-ISF002-2673 National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore), ASPIRE League seed grant Nanyang Technological University (NTU), FYP fund Nanyang Technological University (NTU), iGEM fund Nanyang Technological University (NTU), Ph.D. research scholarship Nanyang Technological University (NTU), Core funds Genome Institute of Singapore (GIS)
Athanasiadis,
Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome.
2004, Pubmed
Athanasiadis,
Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome.
2004,
Pubmed Bahn,
Genomic analysis of ADAR1 binding and its involvement in multiple RNA processing pathways.
2015,
Pubmed Bazak,
A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes.
2014,
Pubmed Begik,
Quantitative profiling of pseudouridylation dynamics in native RNAs with nanopore sequencing.
2021,
Pubmed Boccaletto,
MODOMICS: a database of RNA modification pathways. 2017 update.
2018,
Pubmed Breen,
Global landscape and genetic regulation of RNA editing in cortical samples from individuals with schizophrenia.
2019,
Pubmed Buchumenski,
Systematic identification of A-to-I RNA editing in zebrafish development and adult organs.
2021,
Pubmed Burns,
Regulation of serotonin-2C receptor G-protein coupling by RNA editing.
1997,
Pubmed Chalk,
The majority of A-to-I RNA editing is not required for mammalian homeostasis.
2019,
Pubmed Chen,
Nuclear m6A reader YTHDC1 regulates the scaffold function of LINE1 RNA in mouse ESCs and early embryos.
2021,
Pubmed Cox,
RNA editing with CRISPR-Cas13.
2017,
Pubmed Ding,
Gaussian mixture model-based unsupervised nucleotide modification number detection using nanopore-sequencing readouts.
2020,
Pubmed Dobin,
STAR: ultrafast universal RNA-seq aligner.
2013,
Pubmed Eggington,
Predicting sites of ADAR editing in double-stranded RNA.
2011,
Pubmed Gacem,
ADAR1 mediated regulation of neural crest derived melanocytes and Schwann cell development.
2020,
Pubmed Gannon,
Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells.
2018,
Pubmed Garalde,
Highly parallel direct RNA sequencing on an array of nanopores.
2018,
Pubmed Garrett,
RNA editing underlies temperature adaptation in K+ channels from polar octopuses.
2012,
Pubmed
,
Xenbase Ghandi,
Next-generation characterization of the Cancer Cell Line Encyclopedia.
2019,
Pubmed Han,
The Genomic Landscape and Clinical Relevance of A-to-I RNA Editing in Human Cancers.
2015,
Pubmed Hartner,
Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1.
2004,
Pubmed Hoopengardner,
Nervous system targets of RNA editing identified by comparative genomics.
2003,
Pubmed Hsiao,
RNA editing in nascent RNA affects pre-mRNA splicing.
2018,
Pubmed Ishizuka,
Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade.
2019,
Pubmed Ivanov,
Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals.
2015,
Pubmed Jain,
The Editor's I on Disease Development.
2019,
Pubmed Jenjaroenpun,
Decoding the epitranscriptional landscape from native RNA sequences.
2021,
Pubmed Kawahara,
Redirection of silencing targets by adenosine-to-inosine editing of miRNAs.
2007,
Pubmed Khermesh,
Reduced levels of protein recoding by A-to-I RNA editing in Alzheimer's disease.
2016,
Pubmed Leger,
RNA modifications detection by comparative Nanopore direct RNA sequencing.
2021,
Pubmed Lehmann,
Double-stranded RNA adenosine deaminases ADAR1 and ADAR2 have overlapping specificities.
2000,
Pubmed
,
Xenbase Liddicoat,
RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself.
2015,
Pubmed Liscovitch-Brauer,
Trade-off between Transcriptome Plasticity and Genome Evolution in Cephalopods.
2017,
Pubmed Liu,
Accurate detection of m6A RNA modifications in native RNA sequences.
2019,
Pubmed Liu,
Tumor-derived IFN triggers chronic pathway agonism and sensitivity to ADAR loss.
2019,
Pubmed Liu,
The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity.
2021,
Pubmed Lo Giudice,
Investigating RNA editing in deep transcriptome datasets with REDItools and REDIportal.
2020,
Pubmed Lo Giudice,
Quantifying RNA Editing in Deep Transcriptome Datasets.
2020,
Pubmed Loman,
A complete bacterial genome assembled de novo using only nanopore sequencing data.
2015,
Pubmed Lorenz,
Direct RNA sequencing enables m6A detection in endogenous transcript isoforms at base-specific resolution.
2020,
Pubmed Mannion,
The RNA-editing enzyme ADAR1 controls innate immune responses to RNA.
2014,
Pubmed Mansi,
REDIportal: millions of novel A-to-I RNA editing events from thousands of RNAseq experiments.
2021,
Pubmed McKenna,
The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data.
2010,
Pubmed Merkle,
Precise RNA editing by recruiting endogenous ADARs with antisense oligonucleotides.
2019,
Pubmed Nguyen,
Advancing System Performance with Redundancy: From Biological to Artificial Designs.
2019,
Pubmed Nishikura,
Functions and regulation of RNA editing by ADAR deaminases.
2010,
Pubmed Pestal,
Isoforms of RNA-Editing Enzyme ADAR1 Independently Control Nucleic Acid Sensor MDA5-Driven Autoimmunity and Multi-organ Development.
2015,
Pubmed Picardi,
Profiling RNA editing in human tissues: towards the inosinome Atlas.
2015,
Pubmed Pinto,
Computational approaches for detection and quantification of A-to-I RNA-editing.
2019,
Pubmed Polson,
Preferential selection of adenosines for modification by double-stranded RNA adenosine deaminase.
1994,
Pubmed Porath,
Massive A-to-I RNA editing is common across the Metazoa and correlates with dsRNA abundance.
2017,
Pubmed
,
Xenbase Pratanwanich,
Identification of differential RNA modifications from nanopore direct RNA sequencing with xPore.
2021,
Pubmed Price,
Direct RNA sequencing reveals m6A modifications on adenovirus RNA are necessary for efficient splicing.
2020,
Pubmed Qu,
Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs.
2019,
Pubmed Ramaswami,
RADAR: a rigorously annotated database of A-to-I RNA editing.
2014,
Pubmed Rice,
Mutations in ADAR1 cause Aicardi-Goutières syndrome associated with a type I interferon signature.
2012,
Pubmed Roth,
Increased RNA Editing May Provide a Source for Autoantigens in Systemic Lupus Erythematosus.
2018,
Pubmed Rybak-Wolf,
Circular RNAs in the Mammalian Brain Are Highly Abundant, Conserved, and Dynamically Expressed.
2015,
Pubmed Sakurai,
Inosine cyanoethylation identifies A-to-I RNA editing sites in the human transcriptome.
2010,
Pubmed Shallev,
Decreased A-to-I RNA editing as a source of keratinocytes' dsRNA in psoriasis.
2018,
Pubmed Sherry,
dbSNP-database for single nucleotide polymorphisms and other classes of minor genetic variation.
1999,
Pubmed Sherry,
dbSNP: the NCBI database of genetic variation.
2001,
Pubmed Sommer,
RNA editing in brain controls a determinant of ion flow in glutamate-gated channels.
1991,
Pubmed Stellos,
Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation.
2016,
Pubmed Tan,
Dynamic landscape and regulation of RNA editing in mammals.
2017,
Pubmed Tran,
Widespread RNA editing dysregulation in brains from autistic individuals.
2019,
Pubmed Wang,
Requirement of the RNA editing deaminase ADAR1 gene for embryonic erythropoiesis.
2000,
Pubmed Wang,
Stress-induced apoptosis associated with null mutation of ADAR1 RNA editing deaminase gene.
2004,
Pubmed Wick,
Deepbinner: Demultiplexing barcoded Oxford Nanopore reads with deep convolutional neural networks.
2018,
Pubmed Xiong,
RNA m6A modification orchestrates a LINE-1-host interaction that facilitates retrotransposition and contributes to long gene vulnerability.
2021,
Pubmed Xu,
METTL3 regulates heterochromatin in mouse embryonic stem cells.
2021,
Pubmed Yang,
Modulation of microRNA processing and expression through RNA editing by ADAR deaminases.
2006,
Pubmed Yoshida,
Modification of nucleosides and nucleotides. VII. Selective cyanoethylation of inosine and pseudouridine in yeast transfer ribonucleic acid.
1968,
Pubmed Zhang,
The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs.
2001,
Pubmed
,
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