Human DNA Exonuclease TREX1 Is Also an Exoribonuclease That Acts on Single-stranded RNA |
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| Authors: | Fenghua Yuan Tanmay Dutta Ling Wang Lei Song Liya Gu Liangyue Qian Anaid Benitez Shunbin Ning Arun Malhotra Murray P. Deutscher Yanbin Zhang |
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| Affiliation: | From the ‡Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136.;the §Department of Medicine, Center for Inflammation, Infectious Diseases, and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37614, and ;the ¶Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, Kentucky 40536 |
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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 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. |
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| Keywords: | deoxyribonuclease (DNase) DNA ribonuclease RNA RNA degradation trex1 |
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