Limited RNA Editing in Exons of Mouse Liver and Adipose

Lagarrigue, Sandrine; Hormozdiari, Farhad; Martin, Lisa; Lecerf, Frédéric; Hasin, Yehudit; Rau, Christoph; Hagopian, Raffi; Xiao, Yu; Yan, Jun; Drake, Thomas A.; Ghazalpour, Anatole; Eskin, Eleazar; Lusis, Aldons J.

doi:10.1534/genetics.112.149054

Cited by 24 publications

(32 citation statements)

References 26 publications

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“…Consequently, improved methods to robustly characterize genome-wide RE events (Danecek et al 2012;Ramaswami et al 2012;Picardi and Pesole 2013) have enabled genome-wide characterization of RE in several, mostly nondiseased, tissues (Danecek et al 2012;Park et al 2012;Lagarrigue et al 2013;Bazak et al 2014;Blanc et al 2014;Han et al 2015). To date, however, only a few studies have reported RE events at a genome-wide scale in disease tissues; for example, Han et al (2015) showed that in various cancer types RE events are associated with survival and drug resistance.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of differential RNA editing in epilepsy

et al. 2017

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The recoding of genetic information through RNA editing contributes to proteomic diversity, but the extent and significance of RNA editing in disease is poorly understood. In particular, few studies have investigated the relationship between RNA editing and disease at a genome-wide level. Here, we developed a framework for the genome-wide detection of RNA sites that are differentially edited in disease. Using RNA-sequencing data from 100 hippocampi from mice with epilepsy (pilocarpine-temporal lobe epilepsy model) and 100 healthy control hippocampi, we identified 256 RNA sites (overlapping with 87 genes) that were significantly differentially edited between epileptic cases and controls. The degree of differential RNA editing in epileptic mice correlated with frequency of seizures, and the set of genes differentially RNA-edited between case and control mice were enriched for functional terms highly relevant to epilepsy, including "neuron projection" and "seizures." Genes with differential RNA editing were preferentially enriched for genes with a genetic association to epilepsy. Indeed, we found that they are significantly enriched for genes that harbor nonsynonymous de novo mutations in patients with epileptic encephalopathy and for common susceptibility variants associated with generalized epilepsy. These analyses reveal a functional convergence between genes that are differentially RNA-edited in acquired symptomatic epilepsy and those that contribute risk for genetic epilepsy. Taken together, our results suggest a potential role for RNA editing in the epileptic hippocampus in the occurrence and severity of epileptic seizures.

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Section: Discussionmentioning

confidence: 99%

Genome-wide analysis of differential RNA editing in epilepsy

et al. 2017

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“…Recently, high-throughput RNA-sequencing (RNA-Seq) data were analyzed in multiple studies to identify RNA-DNA mismatches in mammalian mRNAs (Li et al 2011;Bahn et al 2012;Chen et al 2012;Danecek et al 2012;Gu et al 2012;Park et al 2012;Peng et al 2012;Ramaswami et al 2012Ramaswami et al , 2013Dillman et al 2013;Lagarrigue et al 2013). One of the first studies reported a striking list of all 12 types of RNA-DNA differences (RDDs) in human cells (Li et al 2011), while others presented opposing results (Schrider et al 2011;Bahn et al 2012;Danecek et al 2012;Gu et al 2012;Park et al 2012;Peng et al 2012;Ramaswami et al 2012).…”

Section: Introductionmentioning

confidence: 99%

Analysis and design of RNA sequencing experiments for identifying RNA editing and other single-nucleotide variants

Lee

Ang

Xiao

2013

RNA

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RNA-sequencing (RNA-Seq) technologies hold enormous promise for novel discoveries in genomics and transcriptomics. In the past year, a surge of reports has analyzed RNA-Seq data to gain a global view of the RNA editome. Opposing results have been presented, giving rise to extensive debate surrounding one of the first such studies in which a daunting list of all 12 types of RNA-DNA differences (RDDs) were identified. Although a consensus is forming that some of the initial "paradigm-shifting" results of this study may be questionable, recent reports on this topic differed in terms of the number and relative abundance of each type of RDD. Many outstanding issues exist, most importantly, the choice of bioinformatic approaches. Here we discuss the critical data analysis and experimental design issues of such studies to enable improved systematic investigation of the largely unexplored frontier of single-nucleotide variants in RNA.

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“…The highly accurate measurement of transcript abundance by RNA-Seq can also be used to discover novel transcripts and to identify alternative splicing isoforms and RNA-editing events (Graveley 2008;Shendure 2008;Bahn et al 2012). In particular, the depth of sequence read coverage per reference nucleotide enhances the qualities of base calling and can improve the large-scale detection of RNA-editing sites (Bahn et al 2012;Peng et al 2012;Lagarrigue et al 2013;Ramaswami et al 2013). Although the alignment of RNA-Seq reads to a reference genome can infer RNA-editing events, distinguishing these from genomeencoded single nucleotide polymorphisms (SNPs) and technical artifacts caused by sequencing or read-mapping errors is still the major challenge in identifying RNA-editing sites using RNA-Seq data (Ramaswami et al 2013).…”

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confidence: 99%

Abundant and Selective RNA-Editing Events in the Medicinal Mushroom Ganoderma lucidum

et al. 2014

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RNA editing is a widespread, post-transcriptional molecular phenomenon that diversifies hereditary information across various organisms. However, little is known about genome-scale RNA editing in fungi. In this study, we screened for fungal RNA editing sites at the genomic level in Ganoderma lucidum, a valuable medicinal fungus. On the basis of our pipeline that predicted the editing sites from genomic and transcriptomic data, a total of 8906 possible RNA-editing sites were identified within the G. lucidum genome, including the exon and intron sequences and the 59-/39-untranslated regions of 2991 genes and the intergenic regions. The major editing types included C-to-U, A-to-G, G-to-A, and U-to-C conversions. Four putative RNA-editing enzymes were identified, including three adenosine deaminases acting on transfer RNA and a deoxycytidylate deaminase. The genes containing RNA-editing sites were functionally classified by the Kyoto Encyclopedia of Genes and Genomes enrichment and gene ontology analysis. The key functional groupings enriched for RNA-editing sites included laccase genes involved in lignin degradation, key enzymes involved in triterpenoid biosynthesis, and transcription factors. A total of 97 putative editing sites were randomly selected and validated by using PCR and Sanger sequencing. We presented an accurate and large-scale identification of RNA-editing events in G. lucidum, providing global and quantitative cataloging of RNA editing in the fungal genome. This study will shed light on the role of transcriptional plasticity in the growth and development of G. lucidum, as well as its adaptation to the environment and the regulation of valuable secondary metabolite pathways. RNA editing is a post-transcriptional process that can enhance the diversity of gene products by altering RNA sequences. This can involve site-specific nucleotide modifications, nucleotide insertions/deletions, and nucleotide substitutions (Gott and Emeson 2000;Bass 2002;Farajollahi and Maas 2010). RNA editing can affect messenger RNAs (mRNAs), transfer RNAs (tRNAs), ribosomal RNAs, and small regulatory RNAs present in all cellular compartments and has been described in a wide range of organisms from viruses to fungi, mammals, and plants ( Gott and Emeson 2000;Gott 2003;Kawahara et al. 2007). The prevalent RNA-editing pathways in higher eukaryotes involves the deamination of cytidine (C) to create uridine (U) and deamination of adenosine (A) to create inosine (I) (Bass 2002;Gott 2003). The editing process generally involves a specificity factor (RNA or protein) that recognizes the editing site, as well as an enzyme, occasionally with other accessory factors, that catalyzes the reaction (Bass 2002). The functions of RNA editing include regulation of gene expression, increasing protein diversity and reversion of the effect of mutations in the genome (Gott and Emeson 2000;Gott 2003). In many cases, RNA editing is essential for correcting protein production (Young 1990) or for modulating the functional properties of proteins...

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Limited RNA Editing in Exons of Mouse Liver and Adipose

Cited by 24 publications

References 26 publications

Genome-wide analysis of differential RNA editing in epilepsy

Genome-wide analysis of differential RNA editing in epilepsy

Analysis and design of RNA sequencing experiments for identifying RNA editing and other single-nucleotide variants

Abundant and Selective RNA-Editing Events in the Medicinal Mushroom Ganoderma lucidum

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