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 Km 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.

Document Type

Article

Publication Date

5-22-2015

Notes/Citation Information

Published in The Journal of Biological Chemistry, v. 290, no. 21, p. 13344-13353.

This research was originally published in The Journal of Biological Chemistry. Fenghua Yuan, Tanmay Dutta, Ling Wang, Lei Song, Liya Gu, Liangyue Qian, Anaid Benitez, Shunbin Ning, Arun Malhotra, Murray P. Deutscher, and Yanbin Zhang. Human DNA Exonuclease TREX1 Is Also an Exoribonuclease That Acts on Single-Stranded RNA. The Journal of Biological Chemistry. 2015; 290:13344-13353. © the American Society for Biochemistry and Molecular Biology.

The copyright holder has granted the permission for posting the article here.

Digital Object Identifier (DOI)

https://doi.org/10.1074/jbc.M115.653915

Funding Information

This work was supported, in whole or in part, by National Institutes of Health Grants HL105631 (to Y. Z.) and GM16317 (to M. D.).

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