Evidence for Transcriptome-wide RNA Editing Among Sus Scrofa PRE-1 SINE Elements

Overview

Journal BMC Genomics

Publisher Biomed Central

Specialty Genetics

Date 2017 May 11

PMID 28486975

Citations 18

Authors

Scott A Funkhouser

Juan P Steibel

Ronald O Bates

Nancy E Raney

Darius Schenk

Catherine W Ernst

Affiliations

Soon will be listed here.

Abstract

Background: RNA editing by ADAR (adenosine deaminase acting on RNA) proteins is a form of transcriptional regulation that is widespread among humans and other primates. Based on high-throughput scans used to identify putative RNA editing sites, ADAR appears to catalyze a substantial number of adenosine to inosine transitions within repetitive regions of the primate transcriptome, thereby dramatically enhancing genetic variation beyond what is encoded in the genome.

Results: Here, we demonstrate the editing potential of the pig transcriptome by utilizing DNA and RNA sequence data from the same pig. We identified a total of 8550 mismatches between DNA and RNA sequences across three tissues, with 75% of these exhibiting an A-to-G (DNA to RNA) discrepancy, indicative of a canonical ADAR-catalyzed RNA editing event. When we consider only mismatches within repetitive regions of the genome, the A-to-G percentage increases to 94%, with the majority of these located within the swine specific SINE retrotransposon PRE-1. We also observe evidence of A-to-G editing within coding regions that were previously verified in primates.

Conclusions: Thus, our high-throughput evidence suggests that pervasive RNA editing by ADAR can exist outside of the primate lineage to dramatically enhance genetic variation in pigs.

Citing Articles

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Gabay O, Shoshan Y, Kopel E, Ben-Zvi U, Mann T, Bressler N Nat Commun. 2022; 13(1):1184.

PMID: 35246538 PMC: 8897444. DOI: 10.1038/s41467-022-28841-4.

References

Higuchi M, Maas S, Single F, Hartner J, Rozov A, Burnashev N . Point mutation in an AMPA receptor gene rescues lethality in mice deficient in the RNA-editing enzyme ADAR2. Nature. 2000; 406(6791):78-81. DOI: 10.1038/35017558. View

Li H, Ruan J, Durbin R . Mapping short DNA sequencing reads and calling variants using mapping quality scores. Genome Res. 2008; 18(11):1851-8. PMC: 2577856. DOI: 10.1101/gr.078212.108. View

Eisenberg E, Nemzer S, Kinar Y, Sorek R, Rechavi G, Levanon E . Is abundant A-to-I RNA editing primate-specific?. Trends Genet. 2005; 21(2):77-81. DOI: 10.1016/j.tig.2004.12.005. View

Langmead B, Salzberg S . Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012; 9(4):357-9. PMC: 3322381. DOI: 10.1038/nmeth.1923. View

Li H . A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics. 2011; 27(21):2987-93. PMC: 3198575. DOI: 10.1093/bioinformatics/btr509. View

Jurka J, Kapitonov V, Pavlicek A, Klonowski P, Kohany O, Walichiewicz J . Repbase Update, a database of eukaryotic repetitive elements. Cytogenet Genome Res. 2005; 110(1-4):462-7. DOI: 10.1159/000084979. View

Trapnell C, Pachter L, Salzberg S . TopHat: discovering splice junctions with RNA-Seq. Bioinformatics. 2009; 25(9):1105-11. PMC: 2672628. DOI: 10.1093/bioinformatics/btp120. View

Bazak L, Haviv A, Barak M, Jacob-Hirsch J, Deng P, Zhang R . A-to-I RNA editing occurs at over a hundred million genomic sites, located in a majority of human genes. Genome Res. 2013; 24(3):365-76. PMC: 3941102. DOI: 10.1101/gr.164749.113. View

Chen J, Peng Z, Zhang R, Yang X, Chin-Ming Tan B, Fang H . RNA editome in rhesus macaque shaped by purifying selection. PLoS Genet. 2014; 10(4):e1004274. PMC: 3983040. DOI: 10.1371/journal.pgen.1004274. View

10.

Neeman Y, Levanon E, Jantsch M, Eisenberg E . RNA editing level in the mouse is determined by the genomic repeat repertoire. RNA. 2006; 12(10):1802-9. PMC: 1581974. DOI: 10.1261/rna.165106. View

11.

Scadden A, Smith C . RNAi is antagonized by A-->I hyper-editing. EMBO Rep. 2001; 2(12):1107-11. PMC: 1084162. DOI: 10.1093/embo-reports/kve244. View

12.

Blow M, Futreal P, Wooster R, Stratton M . A survey of RNA editing in human brain. Genome Res. 2004; 14(12):2379-87. PMC: 534661. DOI: 10.1101/gr.2951204. View

13.

Kleinman C, Adoue V, Majewski J . RNA editing of protein sequences: a rare event in human transcriptomes. RNA. 2012; 18(9):1586-96. PMC: 3425774. DOI: 10.1261/rna.033233.112. View

14.

Lev-Maor G, Sorek R, Levanon E, Paz N, Eisenberg E, Ast G . RNA-editing-mediated exon evolution. Genome Biol. 2007; 8(2):R29. PMC: 1852406. DOI: 10.1186/gb-2007-8-2-r29. View

15.

Athanasiadis A, Rich A, Maas S . Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLoS Biol. 2004; 2(12):e391. PMC: 526178. DOI: 10.1371/journal.pbio.0020391. View

16.

Bazak L, Levanon E, Eisenberg E . Genome-wide analysis of Alu editability. Nucleic Acids Res. 2014; 42(11):6876-84. PMC: 4066801. DOI: 10.1093/nar/gku414. View

17.

Deffit S, Hundley H . To edit or not to edit: regulation of ADAR editing specificity and efficiency. Wiley Interdiscip Rev RNA. 2015; 7(1):113-27. DOI: 10.1002/wrna.1319. View

18.

Ramaswami G, Lin W, Piskol R, Tan M, Davis C, Li J . Accurate identification of human Alu and non-Alu RNA editing sites. Nat Methods. 2012; 9(6):579-81. PMC: 3662811. DOI: 10.1038/nmeth.1982. View

19.

Benne R, van den Burg J, Brakenhoff J, Sloof P, VAN Boom J, Tromp M . Major transcript of the frameshifted coxII gene from trypanosome mitochondria contains four nucleotides that are not encoded in the DNA. Cell. 1986; 46(6):819-26. DOI: 10.1016/0092-8674(86)90063-2. View

20.

Daniel C, Silberberg G, Behm M, Ohman M . Alu elements shape the primate transcriptome by cis-regulation of RNA editing. Genome Biol. 2014; 15(2):R28. PMC: 4053975. DOI: 10.1186/gb-2014-15-2-r28. View