Mutations involved in Aicardi-Goutières syndrome implicate SAMHD1 as regulator of the innate immune response.
Gillian I. Rice,Jacquelyn Bond,Aruna Asipu,Rebecca L. Brunette,Iain W. Manfield,Ian M. Carr,Jonathan C. Fuller,Richard M. Jackson,Teresa Lamb,Tracy A Briggs,Manir Ali,Hannah Gornall,Lydia R Couthard,Alec Aeby,Simon Attard-Montalto,Enrico Bertini,Christine Bodemer,Knut Brockmann,Louise Brueton,Peter Corry,Isabelle Desguerre,Elisa Fazzi,Angels Garcia Cazorla,Blanca Gener,Ben C.J. Hamel,Arvid Heiberg,Matthew F. Hunter,Marjo S. van der Knaap,Ram L. Kumar,Lieven Lagae,Pierre Landrieu,Charles Marques Lourenço,Daphna Marom,Michael F. McDermott,William G. Van Der Merwe,Simona Orcesi,Julie S. Prendiville,Magnhild Rasmussen,Stavit A. Shalev,Doriette Soler,Marwan Shinawi,Ronen Spiegel,Tiong Yang Tan,Adeline Vanderver,Emma Wakeling,Evangeline Wassmer,Elizabeth Whittaker,Pierre Lebon,Daniel B. Stetson,David T. Bonthron,Yanick J. Crow +50 more
TLDR
Mutations in SAMHD1 are described as the cause of Aicardi-Goutières syndrome at the AGS5 locus and data is presented to show that SAM HD1 may act as a negative regulator of the cell-intrinsic antiviral response.Abstract:
Aicardi-Goutieres syndrome is a mendelian mimic of congenital infection and also shows overlap with systemic lupus erythematosus at both a clinical and biochemical level The recent identification of mutations in TREX1 and genes encoding the RNASEH2 complex and studies of the function of TREX1 in DNA metabolism have defined a previously unknown mechanism for the initiation of autoimmunity by interferon-stimulatory nucleic acid Here we describe mutations in SAMHD1 as the cause of AGS at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral responseread more
Citations
More filters
Journal ArticleDOI
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors
Taro Kawai,Shizuo Akira +1 more
TL;DR: Recent advances that have been made by research into the role of TLR biology in host defense and disease are described.
Journal ArticleDOI
Pattern Recognition Receptors and Inflammation
Osamu Takeuchi,Shizuo Akira +1 more
TL;DR: The role of PRRs, their signaling pathways, and how they control inflammatory responses are discussed.
Journal ArticleDOI
A census of human RNA-binding proteins.
TL;DR: This work presents a census of 1,542 manually curated RBPs that are analysed for their interactions with different classes of RNA, their evolutionary conservation, their abundance and their tissue-specific expression, a critical step towards the comprehensive characterization of proteins involved in human RNA metabolism.
Journal ArticleDOI
SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx
Nadine Laguette,Bijan Sobhian,Nicoletta Casartelli,Mathieu Ringeard,Christine Chable-Bessia,Emmanuel Ségéral,Ahmad Yatim,Stéphane Emiliani,Olivier Schwartz,Monsef Benkirane +9 more
TL;DR: It is demonstrated that SAMHD1 is an antiretroviral protein expressed in cells of the myeloid lineage that inhibits an early step of the viral life cycle, and is probably required for HIV-1 restriction.
Journal ArticleDOI
Evolution and Impact of Subclonal Mutations in Chronic Lymphocytic Leukemia
Dan A. Landau,Scott L. Carter,Petar Stojanov,Petar Stojanov,Aaron McKenna,Kristen E. Stevenson,Michael S. Lawrence,Carrie Sougnez,Chip Stewart,Andrey Sivachenko,Lili Wang,Youzhong Wan,Wandi Zhang,Sachet A. Shukla,Sachet A. Shukla,Alexander R. Vartanov,Stacey M. Fernandes,Gordon Saksena,Kristian Cibulskis,Bethany Tesar,Stacey Gabriel,Nir Hacohen,Nir Hacohen,Matthew Meyerson,Eric S. Lander,Donna Neuberg,Jennifer R. Brown,Jennifer R. Brown,Gad Getz,Gad Getz,Catherine J. Wu,Catherine J. Wu +31 more
TL;DR: Analysis of intratumoral heterogeneity in chronic lymphocytic leukemia cases uncovers patterns of clonal evolution in CLL, providing insights into its stepwise transformation, and links the presence of subclones with adverse clinical outcomes.
References
More filters
Journal ArticleDOI
Trex1 Prevents Cell-Intrinsic Initiation of Autoimmunity
TL;DR: It is shown that single-stranded DNA derived from endogenous retroelements accumulates in Trex1-deficient cells, and thatTrex1 can metabolize reverse-transcribed DNA, and suggest an unanticipated contribution of endogenous Retroelements to autoimmunity.
Journal ArticleDOI
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus.
Yanick J. Crow,Yanick J. Crow,Bruce E. Hayward,Rekha Parmar,Peter Robins,Andrea Leitch,Manir Ali,Deborah N. Black,Hans van Bokhoven,Han G. Brunner,Ben C.J. Hamel,Peter Corry,Frances M. Cowan,S Frints,Joerg Klepper,John H. Livingston,Sally Ann Lynch,Roger F. Massey,Jean François Meritet,Jacques L. Michaud,Gérard Ponsot,Thomas Voit,Pierre Lebon,David T. Bonthron,Andrew P. Jackson,Deborah E. Barnes,Tomas Lindahl +26 more
TL;DR: TREX1, encoding the major mammalian 3′ → 5′ DNA exonuclease, is the AGS1 gene, and AGS-causing mutations result in abrogation of TREX1 enzyme activity, and failure of which results in the triggering of an abnormal innate immune response.
Journal ArticleDOI
Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection.
Yanick J. Crow,Yanick J. Crow,Andrea Leitch,Bruce E. Hayward,Anna Garner,Rekha Parmar,Elen Griffith,Manir Ali,Colin A. Semple,Jean Aicardi,Riyana Babul-Hirji,Clarisse Baumann,Peter Baxter,Enrico Bertini,Kate Chandler,David Chitayat,Daniel Cau,Catherine Dery,Elisa Fazzi,Cyril Goizet,Mary D. King,Joerg Klepper,Didier Lacombe,Giovanni Lanzi,Hermione Lyall,María Luisa Martínez-Frías,Michèle Mathieu,Carole McKeown,Anne Monier,Yvette Oade,Oliver Quarrell,Christopher D. Rittey,R. Curtis Rogers,Amparo Sanchis,John B.P. Stephenson,Uta Tacke,Marianne Till,John Tolmie,Pam Tomlin,Thomas Voit,Bernhard Weschke,C. Geoffrey Woods,Pierre Lebon,David T. Bonthron,Chris P. Ponting,Andrew P. Jackson +45 more
TL;DR: It is shown that AGS can result from mutations in the genes encoding any one of its three subunits, demonstrating a role for ribonuclease H in human neurological disease and suggesting an unanticipated relationship between ribonUClease H2 and the antiviral immune response that warrants further investigation.
Journal ArticleDOI
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus.
Min Ae Lee-Kirsch,Maolian Gong,Dipanjan Chowdhury,Lydia Senenko,Kerstin Engel,Young-Ae Lee,Young-Ae Lee,Udesh de Silva,Suzanna L. Bailey,Torsten Witte,Timothy J. Vyse,Juha Kere,Christiane Pfeiffer,Scott Harvey,Andrew Wong,Sari Koskenmies,Oliver Hummel,Klaus Rohde,Reinhold E. Schmidt,Anna F. Dominiczak,M. Gahr,Thomas Hollis,Fred W. Perrino,Judy Lieberman,Norbert Hubner +24 more
TL;DR: This work reports monoallelic frameshift or missense mutations and one 3′ UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls, and demonstrates that two mutant TREx1 alleles alter subcellular targeting.
Journal ArticleDOI
Trex1 Exonuclease Degrades ssDNA to Prevent Chronic Checkpoint Activation and Autoimmune Disease
TL;DR: It is reported that Trex1, ordinarily associated with the endoplasmic reticulum (ER), relocalizes to the S phase nucleus after gamma irradiation or hydroxyurea treatment and acts on a single-stranded DNA polynucleotide species generated from processing of aberrant replication intermediates to attenuate DNA damage checkpoint signaling and prevent pathological immune activation.
Related Papers (5)
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus.
Yanick J. Crow,Yanick J. Crow,Bruce E. Hayward,Rekha Parmar,Peter Robins,Andrea Leitch,Manir Ali,Deborah N. Black,Hans van Bokhoven,Han G. Brunner,Ben C.J. Hamel,Peter Corry,Frances M. Cowan,S Frints,Joerg Klepper,John H. Livingston,Sally Ann Lynch,Roger F. Massey,Jean François Meritet,Jacques L. Michaud,Gérard Ponsot,Thomas Voit,Pierre Lebon,David T. Bonthron,Andrew P. Jackson,Deborah E. Barnes,Tomas Lindahl +26 more
Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutières syndrome and mimic congenital viral brain infection.
Yanick J. Crow,Yanick J. Crow,Andrea Leitch,Bruce E. Hayward,Anna Garner,Rekha Parmar,Elen Griffith,Manir Ali,Colin A. Semple,Jean Aicardi,Riyana Babul-Hirji,Clarisse Baumann,Peter Baxter,Enrico Bertini,Kate Chandler,David Chitayat,Daniel Cau,Catherine Dery,Elisa Fazzi,Cyril Goizet,Mary D. King,Joerg Klepper,Didier Lacombe,Giovanni Lanzi,Hermione Lyall,María Luisa Martínez-Frías,Michèle Mathieu,Carole McKeown,Anne Monier,Yvette Oade,Oliver Quarrell,Christopher D. Rittey,R. Curtis Rogers,Amparo Sanchis,John B.P. Stephenson,Uta Tacke,Marianne Till,John Tolmie,Pam Tomlin,Thomas Voit,Bernhard Weschke,C. Geoffrey Woods,Pierre Lebon,David T. Bonthron,Chris P. Ponting,Andrew P. Jackson +45 more