Human DNA exonuclease TREX1 is also an exoribonuclease that acts on single-stranded RNA

Fenghua Yuan, Tanmay Dutta, Ling Wang, Lei Song, Liya Gu, Liangyue Qian, Anaid Benitez, Shunbin Ning, Arun Malhotra, Murray P Deutscher, Yanbin Zhang

Research output: Contribution to journalArticle

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Abstract

3′ repair exonuclease 1 (TREX1) is a known DNA exonuclease involved in autoimmune disorders and the antiviral response. In this work, we show that TREX1 is also a RNA exonuclease. Purified TREX1 displays robust exoribonuclease activity that degrades single-stranded, but not double-stranded, RNA. TREX1-D200N, an Aicardi-Goutieres syndrome disease-causing mutant, is defective in degrading RNA. TREX1 activity is strongly inhibited by a stretch of pyrimidine residues as is a bacterial homolog, RNase T. Kinetic measurements indicate that the apparent K<inf>m</inf> of TREX1 for RNA is higher than that for DNA. Like RNase T, human TREX1 is active in degrading native tRNA substrates. Previously reported TREX1 crystal structures have revealed that the substrate binding sites are open enough to accommodate the extra hydroxyl group in RNA, further supporting our conclusion that TREX1 acts on RNA. These findings indicate that its RNase activity needs to be taken into account when evaluating the physiological role of TREX1.

Original languageEnglish (US)
Pages (from-to)13344-13353
Number of pages10
JournalJournal of Biological Chemistry
Volume290
Issue number21
DOIs
StatePublished - May 22 2015

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Exodeoxyribonucleases
Exoribonucleases
RNA
spleen exonuclease
Exonucleases
Double-Stranded RNA
Substrates
Ribonucleases
Transfer RNA
Hydroxyl Radical
Antiviral Agents
Repair
Crystal structure
Display devices
Binding Sites
Kinetics
DNA

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Human DNA exonuclease TREX1 is also an exoribonuclease that acts on single-stranded RNA. / Yuan, Fenghua; Dutta, Tanmay; Wang, Ling; Song, Lei; Gu, Liya; Qian, Liangyue; Benitez, Anaid; Ning, Shunbin; Malhotra, Arun; Deutscher, Murray P; Zhang, Yanbin.

In: Journal of Biological Chemistry, Vol. 290, No. 21, 22.05.2015, p. 13344-13353.

Research output: Contribution to journalArticle

Yuan, F, Dutta, T, Wang, L, Song, L, Gu, L, Qian, L, Benitez, A, Ning, S, Malhotra, A, Deutscher, MP & Zhang, Y 2015, 'Human DNA exonuclease TREX1 is also an exoribonuclease that acts on single-stranded RNA', Journal of Biological Chemistry, vol. 290, no. 21, pp. 13344-13353. https://doi.org/10.1074/jbc.M115.653915
Yuan, Fenghua ; Dutta, Tanmay ; Wang, Ling ; Song, Lei ; Gu, Liya ; Qian, Liangyue ; Benitez, Anaid ; Ning, Shunbin ; Malhotra, Arun ; Deutscher, Murray P ; Zhang, Yanbin. / Human DNA exonuclease TREX1 is also an exoribonuclease that acts on single-stranded RNA. In: Journal of Biological Chemistry. 2015 ; Vol. 290, No. 21. pp. 13344-13353.
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