TY - JOUR
T1 - Human DNA exonuclease TREX1 is also an exoribonuclease that acts on single-stranded RNA
AU - Yuan, Fenghua
AU - Dutta, Tanmay
AU - Wang, Ling
AU - Song, Lei
AU - Gu, Liya
AU - Qian, Liangyue
AU - Benitez, Anaid
AU - Ning, Shunbin
AU - Malhotra, Arun
AU - Deutscher, Murray P.
AU - Zhang, Yanbin
N1 - Publisher Copyright:
© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2015/5/22
Y1 - 2015/5/22
N2 - 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.
AB - 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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U2 - 10.1074/jbc.M115.653915
DO - 10.1074/jbc.M115.653915
M3 - Article
C2 - 25855793
AN - SCOPUS:84930007408
SN - 0021-9258
VL - 290
SP - 13344
EP - 13353
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 21
ER -