title: Human DNA Exonuclease TREX1 Is Also an Exoribonuclease That Acts on Single-stranded RNA.
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.
authors: From the Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136.
authors: Fenghua
authors: http://orcid.org/0000-0002-7999-0750
authors: F
authors: Yuan
authors: From the Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136.
authors: Tanmay
authors: http://orcid.org/0000-0002-0092-345X
authors: T
authors: Dutta
authors: the Department of Medicine, Center for Inflammation, Infectious Diseases, and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37614, and.
authors: Ling
authors: L
authors: Wang
authors: From the Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136.
authors: Lei
authors: L
authors: Song
authors: the Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, Kentucky 40536.
authors: Liya
authors: L
authors: Gu
authors: From the Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136.
authors: Liangyue
authors: L
authors: Qian
authors: From the Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136.
authors: Anaid
authors: A
authors: Benitez
authors: the Department of Medicine, Center for Inflammation, Infectious Diseases, and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37614, and.
authors: Shunbin
authors: S
authors: Ning
authors: From the Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136.
authors: Arun
authors: A
authors: Malhotra
authors: From the Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136.
authors: Murray P
authors: MP
authors: Deutscher
authors: From the Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, Florida 33136, yzhang4@med.miami.edu.
authors: Yanbin
authors: Y
authors: Zhang
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D004247:DNA / Q000378:metabolism; D005090:Exodeoxyribonucleases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005095:Exoribonucleases / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D055503:Protein Multimerization; D012313:RNA / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D010750:Phosphoproteins; D012313:RNA; D004247:DNA; D005090:Exodeoxyribonucleases; D005095:Exoribonucleases; C042081:exoribonuclease T; C429526:three prime repair exonuclease 1
keywords: DNA; RNA; RNA degradation; deoxyribonuclease (DNase); ribonuclease; trex1