title: SAMHD1, the Aicardi-Goutières syndrome gene and retroviral restriction factor, is a phosphorolytic ribonuclease rather than a hydrolytic ribonuclease.
abstract: SAMHD1 plays diverse roles in innate immunity, autoimmune diseases and HIV restriction, but the mechanisms involved are still unclear. SAMHD1 has been reported to have both dNTPase and RNase activities. However, whether SAMHD1 possesses RNase activity remains highly controversial. Here, we found that, unlike conventional hydrolytic exoribonucleases, SAMHD1 requires inorganic phosphate to degrade RNA substrates and produces nucleotide diphosphates rather than nucleoside monophosphates, which indicated that SAMHD1 is a phosphorolytic but not hydrolytic 3'-5' exoribonuclease. Furthermore, SAMHD1 preferentially cleaved single-stranded RNAs comprising A20 or U20, whereas neither C20 nor G20 was susceptible to SAMHD1-mediated degradation. Our findings will facilitate more advanced studies into the role of the SAMHD1 RNase function in the cellular pathogenesis implicated in nucleic acid-triggered inflammatory responses and the anti-retroviral function of SAMHD1.
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Jeongmin
authors.initials: J
authors.lastname: Ryoo
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Sung-Yeon
authors.initials: SY
authors.lastname: Hwang
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Jongsu
authors.initials: J
authors.lastname: Choi
authors.affiliation: Department of the Interdisciplinary Program in Genetic Engineering, Seoul National University, Seoul 08826, Republic of Korea.
authors.forename: Changhoon
authors.initials: C
authors.lastname: Oh
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea. Electronic address: ksahn@snu.ac.kr.
authors.forename: Kwangseog
authors.initials: K
authors.lastname: Ahn
mesh_terms: D020274:Autoimmune Diseases of the Nervous System / Q000201:enzymology*; D001665:Binding Sites; D015226:Dinucleoside Phosphates / Q000737:chemistry*; D004789:Enzyme Activation; D006801:Humans; D006868:Hydrolysis; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry*; D009421:Nervous System Malformations / Q000201:enzymology*; D010766:Phosphorylation; D011485:Protein Binding; D012313:RNA / Q000737:chemistry*; D012191:Retroviridae Proteins / Q000737:chemistry*; D012260:Ribonucleases / Q000737:chemistry*; D000076106:SAM Domain and HD Domain-Containing Protein 1
chemical_list: D015226:Dinucleoside Phosphates; D012191:Retroviridae Proteins; D012313:RNA; D012260:Ribonucleases; D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins
keywords: Exoribonuclease; Phosphorolytic activity; SAMHD1