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. 2010 Nov 30;107(48):20715-9.
doi: 10.1073/pnas.1009231107. Epub 2010 Nov 10.

RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1

Jongchan Yeo  1 , Rena A Goodman, Nicole T Schirle, Sheila S David, Peter A Beal
Affiliations

RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1

Jongchan Yeo et al. Proc Natl Acad Sci U S A. .

Abstract

Editing of the pre-mRNA for the DNA repair enzyme NEIL1 causes a lysine to arginine change in the lesion recognition loop of the protein. The two forms of NEIL1 are shown here to have distinct enzymatic properties. The edited form removes thymine glycol from duplex DNA 30 times more slowly than the form encoded in the genome, whereas editing enhances repair of the guanidinohydantoin lesion by NEIL1. In addition, we show that the NEIL1 recoding site is a preferred editing site for the RNA editing adenosine deaminase ADAR1. The edited adenosine resides in an A-C mismatch in a hairpin stem formed by pairing of exon 6 to the immediate upstream intron 5 sequence. As expected for an ADAR1 site, editing at this position is increased in human cells treated with interferon α. These results suggest a unique regulatory mechanism for DNA repair and extend our understanding of the impact of RNA editing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Known substrates for the base excision repair glycosylase NEIL1. Abbreviations: 5-OHU, 5-hydroxyuracil; DHU, dihydrouracil; 5-OHC, 5-hydroxycytosine; Tg, thymine glycol; Gh, guanidinohydantoin; DHT, dihydrothymine; FapyG, 2,6-diamino-4-hydroxy-5-formamidopyrimidine; Sp, spiroiminodihydantoin; and FapyA, 4,6-diamino-5-formamidopyrimidine.
Fig. 2.
Fig. 2.
(A) Superposition of human NEIL1 structure (dark gray) with that of E. coli Fpg (green) bound to 8-oxoguanine-containing DNA (17, 19). Red open arrow indicates lesion recognition loop of Fpg. (B) Sequence alignment of Fpg/Nei family of DNA repair glycosylases indicating the position of the hNEIL1 recoding site and lesion recognition loop as identified by Imamura, Wallace, and Doublie (18, 22).
Fig. 3.
Fig. 3.
DNA substrates evaluated in this study.
Fig. 4.
Fig. 4.
(A) Predicted RNA secondary structure surrounding NEIL1 recoding site. Lower case lettering indicates intron. (B) In vitro editing of a 200 nt substrate comprising the NEIL1 recoding site. (Left) Sequence of products from reaction of 1 μM human ADAR1. (Right) Sequence of products from reaction of 1 μM human ADAR2. (C) Quantification of editing efficiency of ADAR1 and ADAR2 on model RNA substrate. Red bars: central adenosine of K242 codon, Blue bars: third adenosine of K242 codon. Results are presented as an average % editing and standard deviation from three independent experiments.
Fig. 5.
Fig. 5.
(Top) Mutations made to test RNA secondary structure prediction for NEIL1 recoding site. (Bottom) Quantification of editing efficiency of ADAR1 with different RNA substrates. Red bars: central adenosine of K242 codon, Blue bars: third adenosine of K242 codon. Results are presented as an average % editing and standard deviation from three independent experiments.
Fig. 6.
Fig. 6.
NEIL1 editing in response to IFN-α. (Left) Sequence at the recoding site in NEIL1 cDNA from U87 human glioblastoma cells cultured in the absence of IFN-α. (Right) NEIL1 cDNA sequence from U87 cells treated with IFN-α.
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References

    1. Grosjean H, Benne R. Modification and editing of RNA. Washington, D.C.: ASM Press; 1998.
    1. Higuchi M, et al. RNA editing of AMPA receptor subunit GluR-B: a base-paired intron-exon structure determines position and efficiency. Cell. 1993;75:1361–1370. - PubMed
    1. Burns CM, et al. Regulation of serotonin-2C receptor G-protein coupling by RNA editing. Nature. 1997;387(6630):303–308. - PubMed
    1. Athanasiadis A, Rich A, Maas S. Widespread A-to-I RNA editing of Alu-containing mRNAs in the human transcriptome. PLos Biol. 2004;2:e391. - PMC - PubMed
    1. Barak M, et al. Evidence for large diversity in the human transcriptome created by Alu RNA editing. Nucleic Acids Res. 2009;37:6905–6915. - PMC - PubMed

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