气候变化领域集成服务门户(CCPortal): SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cell-autonomous translational repression

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DOI	10.1073/pnas.2110190118
	SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cell-autonomous translational repression
	Russell A.J.; Gray P.E.; Ziegler J.B.; Kim Y.J.; Smith S.; Sewell W.A.; Goodnow C.C.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:34
英文摘要	Sterile α motif domain-containing protein 9-like (SAMD9L) is encoded by a hallmark interferon-induced gene with a role in controlling virus replication that is not well understood. Here, we analyze SAMD9L function from the perspective of human mutations causing neonatal-onset severe autoinflammatory disease. Whole-genome sequencing of two children with leukocytoclastic panniculitis, basal ganglia calcifications, raised blood inflammatory markers, neutrophilia, anemia, thrombocytopaenia, and almost no B cells revealed heterozygous de novo SAMD9L mutations, p.Asn885Thrfs6 and p.Lys878Serfs13. These frameshift mutations truncate the SAMD9L protein within a domain a region of homology to the nucleotide-binding and oligomerization domain (NOD) of APAF1, ∼80 amino acids C-terminal to the Walker B motif. Single-cell analysis of human cells expressing green fluorescent protein (GFP)-SAMD9L fusion proteins revealed that enforced expression of wild-type SAMD9L repressed translation of red fluorescent protein messenger RNA and globally repressed endogenous protein translation, cell autonomously and in proportion to the level of GFP-SAMD9L in each cell. The children’s truncating mutations dramatically exaggerated translational repression even at low levels of GFP-SAMD9L per cell, as did a missense Arg986Cys mutation reported recurrently as causing ataxia pancytopenia syndrome. Autoinflammatory disease associated with SAMD9L truncating mutations appears to result from an interferon-induced translational repressor whose activity goes unchecked by the loss of C-terminal domains that may normally sense virus infection. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autoinflammatory disease; Nucleotide-binding and oligomerization domain; Pathogen-associated molecular pattern receptor; Translational repression; Virus sensing
语种	英语
scopus关键词	SAMD9L protein, human; tumor suppressor protein; ataxia; case report; child; female; gene expression regulation; genetics; heterozygote; human; male; missense mutation; myelodysplastic syndrome; newborn; pancytopenia; pathology; protein synthesis; Ataxia; Child; Female; Gene Expression Regulation; Heterozygote; Humans; Infant, Newborn; Male; Mutation, Missense; Myelodysplastic Syndromes; Pancytopenia; Protein Biosynthesis; Tumor Suppressor Proteins
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251038
作者单位	Immunogenomics Laboratory, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; Sydney Children’s Hospital, Randwick, NSW 2031, Australia; School of Women’s and Children’s Health, University of New South Wales, Sydney, NSW 2010, Australia; Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, South Korea; SydPath, St Vincent’s Hospital, Darlinghurst, NSW 2010, Australia; Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia
推荐引用方式 GB/T 7714	Russell A.J.,Gray P.E.,Ziegler J.B.,et al. SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cell-autonomous translational repression[J],2021,118(34).
APA	Russell A.J..,Gray P.E..,Ziegler J.B..,Kim Y.J..,Smith S..,...&Goodnow C.C..(2021).SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cell-autonomous translational repression.Proceedings of the National Academy of Sciences of the United States of America,118(34).
MLA	Russell A.J.,et al."SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cell-autonomous translational repression".Proceedings of the National Academy of Sciences of the United States of America 118.34(2021).