Home LiteratureArticle Details
PMID: 21596952 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Widespread RNA and DNA sequence differences in the human transcriptome.

Science (New York, N.Y.) ·Vol. 333 ·No. 6038 ·2011-07-01 ·Pages 53-8

Li M, Wang IX, Li Y, Bruzel A, Richards AL, Toung JM, Cheung VG

Abstract

The transmission of information from DNA to RNA is a critical process. We compared RNA sequences from human B cells of 27 individuals to the corresponding DNA sequences from the same individuals and uncovered more than 10,000 exonic sites where the RNA sequences do not match that of the DNA. All 12 possible categories of discordances were observed. These differences were nonrandom as many sites were found in multiple individuals and in different cell types, including primary skin cells and brain tissues. Using mass spectrometry, we detected peptides that are translated from the discordant RNA sequences and thus do not correspond exactly to the DNA sequences. These widespread RNA-DNA differences in the human transcriptome provide a yet unexplored aspect of genome variation.

MeSH Terms
Adult Aged Amino Acid Sequence B-Lymphocytes Base Sequence Cell Line Cerebral Cortex/cytology DNA/chemistry,genetics Exons Expressed Sequence Tags Fibroblasts Gene Expression Profiling Genetic Variation Genome, Human Genotype Humans Mass Spectrometry Middle Aged Molecular Sequence Data Polymorphism, Single Nucleotide Protein Biosynthesis Proteins/chemistry Proteome/chemistry RNA, Messenger/chemistry,genetics Sequence Analysis, DNA Sequence Analysis, RNA Skin/cytology Untranslated Regions
Chemicals
Proteins Proteome RNA, Messenger Untranslated Regions DNA
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Li Mingyao
Department of Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Wang Isabel X
Li Yun
Bruzel Alan
Richards Allison L
Toung Jonathan M
Cheung Vivian G
References (38)
38 references, click to expand
  1. Functions and regulation of RNA editing by ADAR deaminases.
    Annu Rev Biochem. 2010;79:321-49 PMID: 20192758
  2. Control of kinetic properties of AMPA receptor channels by nuclear RNA editing.
    Science. 1994 Dec 9;266(5191):1709-13 PMID: 7992055
  3. Incomplete editing of rps12 transcripts results in the synthesis of polymorphic polypeptides in plant mitochondria.
    Plant Cell. 1996 Jan;8(1):107-17 PMID: 8597655
  4. Systematic identification of abundant A-to-I editing sites in the human transcriptome.
    Nat Biotechnol. 2004 Aug;22(8):1001-5 PMID: 15258596
  5. Identification of pathways associated with invasive behavior by ovarian cancer cells using multidimensional protein identification technology (MudPIT).
    Mol Biosyst. 2008 Jul;4(7):762-73 PMID: 18563251
  6. Structural basis of transcription: backtracked RNA polymerase II at 3.4 angstrom resolution.
    Science. 2009 May 29;324(5931):1203-6 PMID: 19478184
  7. Accurate whole human genome sequencing using reversible terminator chemistry.
    Nature. 2008 Nov 6;456(7218):53-9 PMID: 18987734
  8. RNA polymerase fidelity and transcriptional proofreading.
    Curr Opin Struct Biol. 2009 Dec;19(6):732-9 PMID: 19914059
  9. Underediting of glutamate receptor GluR-B mRNA in malignant gliomas.
    Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14687-92 PMID: 11717408
  10. CEPH maps.
    Curr Opin Genet Dev. 1992 Jun;2(3):393-9 PMID: 1504612
  11. The role of RNA polymerase in transcriptional fidelity.
    Mol Microbiol. 1991 May;5(5):999-1004 PMID: 1659650
  12. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  13. A map of human genome variation from population-scale sequencing.
    Nature. 2010 Oct 28;467(7319):1061-73 PMID: 20981092
  14. A 3.9-centimorgan-resolution human single-nucleotide polymorphism linkage map and screening set.
    Am J Hum Genet. 2003 Aug;73(2):271-84 PMID: 12844283
  15. Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation.
    Nat Biotechnol. 2010 May;28(5):511-5 PMID: 20436464
  16. Transcriptional fidelity and proofreading by RNA polymerase II.
    Cell. 1998 May 15;93(4):627-37 PMID: 9604937
  17. GENCODE: producing a reference annotation for ENCODE.
    Genome Biol. 2006;7 Suppl 1:S4.1-9 PMID: 16925838
  18. RNA editing: cytidine to uridine conversion in apolipoprotein B mRNA.
    Biochim Biophys Acta. 2000 Nov 15;1494(1-2):1-13 PMID: 11072063
  19. Glutamate receptor RNA editing in vitro by enzymatic conversion of adenosine to inosine.
    Science. 1995 Mar 10;267(5203):1491-4 PMID: 7878468
  20. Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome.
    PLoS Biol. 2004 Dec;2(12):e391 PMID: 15534692
  21. Transcript-assisted transcriptional proofreading.
    Science. 2006 Jul 28;313(5786):518-20 PMID: 16873663
  22. Centre d'etude du polymorphisme humain (CEPH): collaborative genetic mapping of the human genome.
    Genomics. 1990 Mar;6(3):575-7 PMID: 2184120
  23. Inosine cyanoethylation identifies A-to-I RNA editing sites in the human transcriptome.
    Nat Chem Biol. 2010 Oct;6(10):733-40 PMID: 20835228
  24. Transcriptome genetics using second generation sequencing in a Caucasian population.
    Nature. 2010 Apr 1;464(7289):773-7 PMID: 20220756
  25. A haplotype map of the human genome.
    Nature. 2005 Oct 27;437(7063):1299-320 PMID: 16255080
  26. More than 100,000 detectable peptide species elute in single shotgun proteomics runs but the majority is inaccessible to data-dependent LC-MS/MS.
    J Proteome Res. 2011 Apr 1;10(4):1785-93 PMID: 21309581
  27. Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing.
    Science. 2009 May 29;324(5931):1210-3 PMID: 19478186
  28. Transcriptome-wide sequencing reveals numerous APOBEC1 mRNA-editing targets in transcript 3' UTRs.
    Nat Struct Mol Biol. 2011 Feb;18(2):230-6 PMID: 21258325
  29. Apolipoprotein B-48 is the product of a messenger RNA with an organ-specific in-frame stop codon.
    Science. 1987 Oct 16;238(4825):363-6 PMID: 3659919
  30. An unwinding activity that covalently modifies its double-stranded RNA substrate.
    Cell. 1988 Dec 23;55(6):1089-98 PMID: 3203381
  31. Regulation of serotonin-2C receptor G-protein coupling by RNA editing.
    Nature. 1997 May 15;387(6630):303-8 PMID: 9153397
  32. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  33. A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine.
    Cell. 1987 Sep 11;50(6):831-40 PMID: 3621347
  34. Regulation of alternative splicing by RNA editing.
    Nature. 1999 May 6;399(6731):75-80 PMID: 10331393
  35. C. elegans and H. sapiens mRNAs with edited 3' UTRs are present on polysomes.
    RNA. 2008 Oct;14(10):2050-60 PMID: 18719245
  36. The International HapMap Project.
    Nature. 2003 Dec 18;426(6968):789-96 PMID: 14685227
  37. The AID/APOBEC family of nucleic acid mutators.
    Genome Biol. 2008;9(6):229 PMID: 18598372
  38. Status of complete proteome analysis by mass spectrometry: SILAC labeled yeast as a model system.
    Genome Biol. 2006;7(6):R50 PMID: 16784548
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1207018
Published
2011-07-01
Epub
2011-00-19
Pages
53-8
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3204392
Subset
IM
Grants
NHGRI NIH HHS · R01 HG005854 · United States
NHGRI NIH HHS · R01 HG005854-01 · United States
Howard Hughes Medical Institute · United States
Databases
GEO
GSE25840
Corrections
CommentIn
PMID: 22076505
CommentIn
PMID: 22422962
CommentIn
PMID: 22422963
CommentIn
PMID: 22422964
CommentIn
PMID: 22567189
External Links
PubMed source DOI: 10.1126/science.1207018 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2