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PMID: 21258325 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Transcriptome-wide sequencing reveals numerous APOBEC1 mRNA-editing targets in transcript 3' UTRs.

Nature structural & molecular biology ·Vol. 18 ·No. 2 ·2011-02-00 ·Pages 230-6

Rosenberg BR, Hamilton CE, Mwangi MM, Dewell S, Papavasiliou FN

Abstract

Apolipoprotein B-editing enzyme, catalytic polypeptide-1 (APOBEC1) is a cytidine deaminase initially identified by its activity in converting a specific cytidine (C) to uridine (U) in apolipoprotein B (apoB) mRNA transcripts in the small intestine. Editing results in the translation of a truncated apoB isoform with distinct functions in lipid transport. To address the possibility that APOBEC1 edits additional mRNAs, we developed a transcriptome-wide comparative RNA sequencing (RNA-Seq) screen. We identified and validated 32 previously undescribed mRNA targets of APOBEC1 editing, all of which are located in AU-rich segments of transcript 3' untranslated regions (3' UTRs). Further analysis established several characteristic sequence features of editing targets, which were predictive for the identification of additional APOBEC1 substrates. The transcriptomics approach to RNA editing presented here dramatically expands the list of APOBEC1 mRNA editing targets and reveals a novel cellular mechanism for the modification of transcript 3' UTRs.

MeSH Terms
3' Untranslated Regions APOBEC-1 Deaminase Animals Base Sequence Cytidine Deaminase/genetics Gene Expression Profiling Mice Mice, Inbred C57BL RNA Editing RNA, Messenger/genetics
Chemicals
3' Untranslated Regions RNA, Messenger APOBEC-1 Deaminase Apobec1 protein, mouse Cytidine Deaminase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Rosenberg Brad R
Laboratory of Lymphocyte Biology, The Rockefeller University, New York, New York, USA.
Hamilton Claire E
Mwangi Michael M
Dewell Scott
Papavasiliou F Nina
References (59)
59 references, click to expand
  1. Molecular cloning of an apolipoprotein B messenger RNA editing protein.
    Science. 1993 Jun 18;260(5115):1816-9 PMID: 8511591
  2. Hypothesis: RNA editing of microRNA target sites in humans?
    RNA. 2007 Apr;13(4):463-7 PMID: 17255198
  3. Control of kinetic properties of AMPA receptor channels by nuclear RNA editing.
    Science. 1994 Dec 9;266(5191):1709-13 PMID: 7992055
  4. Superior role of apolipoprotein B48 over apolipoprotein B100 in chylomicron assembly and fat absorption: an investigation of apobec-1 knock-out and wild-type mice.
    Biochem J. 2001 Jun 15;356(Pt 3):821-7 PMID: 11389690
  5. Molecular cloning of a human small intestinal apolipoprotein B mRNA editing protein.
    Nucleic Acids Res. 1994 May 25;22(10):1874-9 PMID: 8208612
  6. Purification and molecular cloning of a novel essential component of the apolipoprotein B mRNA editing enzyme-complex.
    J Biol Chem. 2000 Jun 30;275(26):19848-56 PMID: 10781591
  7. Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing.
    Science. 2009 May 29;324(5931):1210-3 PMID: 19478186
  8. 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
  9. A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome.
    Science. 2008 Aug 15;321(5891):956-60 PMID: 18599741
  10. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
    Genome Biol. 2009;10(3):R25 PMID: 19261174
  11. Strong conservation of non-coding sequences during vertebrates evolution: potential involvement in post-transcriptional regulation of gene expression.
    Nucleic Acids Res. 1993 May 25;21(10):2315-22 PMID: 8506129
  12. MicroRNA targeting specificity in mammals: determinants beyond seed pairing.
    Mol Cell. 2007 Jul 6;27(1):91-105 PMID: 17612493
  13. Comparison of the differential context-dependence of DNA deamination by APOBEC enzymes: correlation with mutation spectra in vivo.
    J Mol Biol. 2004 Mar 26;337(3):585-96 PMID: 15019779
  14. RNA editing by adenosine deaminases that act on RNA.
    Annu Rev Biochem. 2002;71:817-46 PMID: 12045112
  15. Adenosine deamination in human transcripts generates novel microRNA binding sites.
    Hum Mol Genet. 2009 Dec 15;18(24):4801-7 PMID: 19776031
  16. apobec-1, the catalytic subunit of the mammalian apolipoprotein B mRNA editing enzyme, is a novel RNA-binding protein.
    J Biol Chem. 1995 Jun 16;270(24):14762-7 PMID: 7782342
  17. Systematic identification of abundant A-to-I editing sites in the human transcriptome.
    Nat Biotechnol. 2004 Aug;22(8):1001-5 PMID: 15258596
  18. Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes.
    Genome Res. 2005 Aug;15(8):1034-50 PMID: 16024819
  19. The neurofibromatosis type I messenger RNA undergoes base-modification RNA editing.
    Nucleic Acids Res. 1996 Feb 1;24(3):478-85 PMID: 8602361
  20. Apolipoprotein B mRNA sequences 3' of the editing site are necessary and sufficient for editing and editosome assembly.
    Nucleic Acids Res. 1991 Dec 25;19(24):6781-6 PMID: 1762908
  21. Hyperediting of multiple cytidines of apolipoprotein B mRNA by APOBEC-1 requires auxiliary protein(s) but not a mooring sequence motif.
    J Biol Chem. 1996 May 10;271(19):11506-10 PMID: 8626710
  22. Overexpression of APOBEC-1 results in mooring sequence-dependent promiscuous RNA editing.
    J Biol Chem. 1996 Feb 9;271(6):3011-7 PMID: 8621694
  23. Proteome diversification by adenosine to inosine RNA editing.
    RNA Biol. 2010 Mar-Apr;7(2):205-12 PMID: 20200492
  24. C-->U editing of neurofibromatosis 1 mRNA occurs in tumors that express both the type II transcript and apobec-1, the catalytic subunit of the apolipoprotein B mRNA-editing enzyme.
    Am J Hum Genet. 2002 Jan;70(1):38-50 PMID: 11727199
  25. Apolipoprotein B RNA sequence 3' of the mooring sequence and cellular sources of auxiliary factors determine the location and extent of promiscuous editing.
    Nucleic Acids Res. 1998 Apr 1;26(7):1644-52 PMID: 9512534
  26. The fate of dsRNA in the nucleus: a p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs.
    Cell. 2001 Aug 24;106(4):465-75 PMID: 11525732
  27. Evolution of the AID/APOBEC family of polynucleotide (deoxy)cytidine deaminases.
    Mol Biol Evol. 2005 Feb;22(2):367-77 PMID: 15496550
  28. Fitting a mixture model by expectation maximization to discover motifs in biopolymers.
    Proc Int Conf Intell Syst Mol Biol. 1994;2:28-36 PMID: 7584402
  29. The p27 catalytic subunit of the apolipoprotein B mRNA editing enzyme is a cytidine deaminase.
    J Biol Chem. 1993 Oct 5;268(28):20709-12 PMID: 8407891
  30. The transcriptional landscape of the yeast genome defined by RNA sequencing.
    Science. 2008 Jun 6;320(5881):1344-9 PMID: 18451266
  31. TopHat: discovering splice junctions with RNA-Seq.
    Bioinformatics. 2009 May 1;25(9):1105-11 PMID: 19289445
  32. Evolutionary origins of apoB mRNA editing: catalysis by a cytidine deaminase that has acquired a novel RNA-binding motif at its active site.
    Cell. 1995 Apr 21;81(2):187-95 PMID: 7736571
  33. Using galaxy to perform large-scale interactive data analyses.
    Curr Protoc Bioinformatics. 2007 Sep;Chapter 10:Unit 10.5 PMID: 18428782
  34. Alu element-mediated gene silencing.
    EMBO J. 2008 Jun 18;27(12):1694-705 PMID: 18497743
  35. Targeted disruption of the mouse apobec-1 gene abolishes apolipoprotein B mRNA editing and eliminates apolipoprotein B48.
    J Biol Chem. 1996 Apr 26;271(17):9887-90 PMID: 8626621
  36. WebLogo: a sequence logo generator.
    Genome Res. 2004 Jun;14(6):1188-90 PMID: 15173120
  37. Sequence requirements for the editing of apolipoprotein B mRNA.
    J Biol Chem. 1991 Sep 5;266(25):16301-4 PMID: 1885564
  38. Apolipoprotein B RNA editing enzyme-deficient mice are viable despite alterations in lipoprotein metabolism.
    Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7154-9 PMID: 8692961
  39. AU-rich elements and associated factors: are there unifying principles?
    Nucleic Acids Res. 2006 Jan 03;33(22):7138-50 PMID: 16391004
  40. Mapping short DNA sequencing reads and calling variants using mapping quality scores.
    Genome Res. 2008 Nov;18(11):1851-8 PMID: 18714091
  41. A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine.
    Cell. 1987 Sep 11;50(6):831-40 PMID: 3621347
  42. Mapping and quantifying mammalian transcriptomes by RNA-Seq.
    Nat Methods. 2008 Jul;5(7):621-8 PMID: 18516045
  43. Alternative mRNA splicing and differential promoter utilization determine tissue-specific expression of the apolipoprotein B mRNA-editing protein (Apobec1) gene in mice. Structure and evolution of Apobec1 and related nucleoside/nucleotide deaminases.
    J Biol Chem. 1995 Jun 2;270(22):13042-56 PMID: 7768898
  44. Genome-wide analysis of allelic expression imbalance in human primary cells by high-throughput transcriptome resequencing.
    Hum Mol Genet. 2010 Jan 1;19(1):122-34 PMID: 19825846
  45. Dimeric structure of a human apolipoprotein B mRNA editing protein and cloning and chromosomal localization of its gene.
    Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8522-6 PMID: 8078915
  46. Apolipoprotein B mRNA-editing protein induces hepatocellular carcinoma and dysplasia in transgenic animals.
    Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8483-7 PMID: 7667315
  47. Cloning and characterization of the rat apobec-1 gene: a comparative analysis of gene structure and promoter usage in rat and mouse.
    J Lipid Res. 1997 Jun;38(6):1103-19 PMID: 9215539
  48. Molecular cloning of apobec-1 complementation factor, a novel RNA-binding protein involved in the editing of apolipoprotein B mRNA.
    Mol Cell Biol. 2000 Mar;20(5):1846-54 PMID: 10669759
  49. The Sequence Alignment/Map format and SAMtools.
    Bioinformatics. 2009 Aug 15;25(16):2078-9 PMID: 19505943
  50. Regulating gene expression through RNA nuclear retention.
    Cell. 2005 Oct 21;123(2):249-63 PMID: 16239143
  51. Enzymatic conversion of adenosine to inosine and to N1-methylinosine in transfer RNAs: a review.
    Biochimie. 1996;78(6):488-501 PMID: 8915538
  52. Widespread cleavage of A-to-I hyperediting substrates.
    RNA. 2009 Sep;15(9):1632-9 PMID: 19622679
  53. The challenge of target sequence specificity in C-->U RNA editing.
    J Clin Invest. 2002 Feb;109(3):291-4 PMID: 11827986
  54. Sequence Searcher: A Java tool to perform regular expression and fuzzy searches of multiple DNA and protein sequences.
    BMC Res Notes. 2009 Jan 30;2:14 PMID: 19183477
  55. Diversity and evolution of mitochondrial RNA editing systems.
    IUBMB Life. 2003 Apr-May;55(4-5):227-33 PMID: 12880203
  56. Detection of single nucleotide variations in expressed exons of the human genome using RNA-Seq.
    Nucleic Acids Res. 2009 Sep;37(16):e106 PMID: 19528076
  57. Three distinct RNA sequence elements are required for efficient apolipoprotein B (apoB) RNA editing in vitro.
    Nucleic Acids Res. 1992 Nov 25;20(22):6007-14 PMID: 1461733
  58. Intestinal lipoprotein assembly in apobec-1-/- mice reveals subtle alterations in triglyceride secretion coupled with a shift to larger lipoproteins.
    Am J Physiol Gastrointest Liver Physiol. 2003 Oct;285(4):G735-46 PMID: 12816761
  59. Nuclear antisense RNA induces extensive adenosine modifications and nuclear retention of target transcripts.
    Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3542-7 PMID: 9108012
Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
Published
2011-02-00
Epub
2011-00-23
Pages
230-6
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC3075553
Subset
IM
Grants
NCI NIH HHS · R01 CA098495-06A2 · United States
NIGMS NIH HHS · GM07739 · United States
NCRR NIH HHS · UL1RR024143 · United States
NCRR NIH HHS · UL1 RR024143 · United States
NCI NIH HHS · R01 CA098495 · United States
NIGMS NIH HHS · T32 GM007739 · United States
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