SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cell-autonomous translational repression

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...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 118; no. 34; pp. 1 - 11
Main Authors Russell, Amanda J., Gray, Paul E., Ziegler, John B., Kim, Yae Jean, Smith, Sandy, Sewell, William A., Goodnow, Christopher C.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 24.08.2021
Subjects
Online AccessGet full text

Cover

Loading…
Abstract 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.Asn885Thrfs*6 and p.Lys878Serfs*13. 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 ofwild-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.
AbstractList The experiments here advance understanding of the function of the SAMD9L gene and protein in innate immune mechanisms in resisting virus infection and in the pathogenesis of inflammatory, hematological, and neurological disorders. The clinical syndrome defined in two children with de novo truncating SAMD9L mutations expands the phenotypes in this newly recognized autoinflammatory disorder. Analysis of cells expressing normal or mutant SAMD9L reveals the protein represses protein translation, with the truncating mutations greatly exaggerating this activity. The experiments find equally potent gain of function caused by the truncating mutations or a recurrent missense mutation associated with clinically milder ataxia and pancytopenia syndromes, demonstrating that diverse clinical manifestations can arise from mutations that appear cell-biologically equivalent. 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.Asn885Thrfs*6 and p.Lys878Serfs*13. 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.
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.Asn885Thrfs*6 and p.Lys878Serfs*13. 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.
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.Asn885Thrfs*6 and p.Lys878Serfs*13. 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 ofwild-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.
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 mutations, p.Asn885Thrfs*6 and p.Lys878Serfs*13. 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.
Author Russell, Amanda J.
Goodnow, Christopher C.
Sewell, William A.
Gray, Paul E.
Ziegler, John B.
Kim, Yae Jean
Smith, Sandy
Author_xml – sequence: 1
  givenname: Amanda J.
  surname: Russell
  fullname: Russell, Amanda J.
– sequence: 2
  givenname: Paul E.
  surname: Gray
  fullname: Gray, Paul E.
– sequence: 3
  givenname: John B.
  surname: Ziegler
  fullname: Ziegler, John B.
– sequence: 4
  givenname: Yae Jean
  surname: Kim
  fullname: Kim, Yae Jean
– sequence: 5
  givenname: Sandy
  surname: Smith
  fullname: Smith, Sandy
– sequence: 6
  givenname: William A.
  surname: Sewell
  fullname: Sewell, William A.
– sequence: 7
  givenname: Christopher C.
  surname: Goodnow
  fullname: Goodnow, Christopher C.
BackLink https://www.ncbi.nlm.nih.gov/pubmed/34417303$$D View this record in MEDLINE/PubMed
BookMark eNpdkUFv1DAQhS1URLeFMydQJC69pB3HdmJfkKq2QKVFHICzNXEcyCqxg-1U7L-vt1uWwmk0mm-e3tM7IUfOO0vIawrnFBp2MTuM5xWlQBVQKp-RFQVFy5orOCIrgKopJa_4MTmJcQMASkh4QY4Z57RhwFYkfL38fK3WBS7JD64fcZow-bAtfCgw4e8Bixmd2SY_W5eXbogWoy2mJWEavIsFmjTcYbKFseNY7nScn_wSixTQxfGBwrEIdg42xry8JM97HKN99ThPyfcPN9-uPpXrLx9vry7XpcmOZVmD7ZA30ghj2o6D6gRQyXvbMF6ZGjvb0SrHMG1PBROyF0qIVkBr6lrKtmWn5P1ed17ayXbGuuxo1HMYJgxb7XHQ_17c8FP_8HdacmCKQhY4exQI_tdiY9LTEHcp0dkcUFeizlaAC5HRd_-hG7-EnPuBErVsVM0zdbGnTPAxBtsfzFDQuz71rk_9t8_88fZphgP_p8AMvNkDm5hrO9yrBppsi7F73xmqvA
CitedBy_id crossref_primary_10_1016_j_yexcr_2023_113541
crossref_primary_10_1111_pai_13711
crossref_primary_10_1073_pnas_2116550119
crossref_primary_10_1016_j_imlet_2022_07_001
crossref_primary_10_1002_bies_202300022
crossref_primary_10_1136_annrheumdis_2021_221486
crossref_primary_10_1111_pde_15411
crossref_primary_10_1038_s41598_021_02489_4
crossref_primary_10_1371_journal_pbio_3002696
crossref_primary_10_1007_s12519_024_00811_4
crossref_primary_10_1002_cnr2_1797
crossref_primary_10_1080_1744666X_2022_2078704
crossref_primary_10_1172_JCI158869
crossref_primary_10_1007_s11845_023_03500_9
crossref_primary_10_24287_1726_1708_2022_21_3_126_135
crossref_primary_10_1111_imm_13579
crossref_primary_10_1111_ped_15283
crossref_primary_10_1126_sciadv_adh8502
Cites_doi 10.1128/JVI.01329-18
10.1111/jns.12409
10.1093/nar/gkt473
10.1038/nmeth.1314
10.1172/JCI129301
10.1128/mBio.01122-15
10.1128/JVI.02262-14
10.1021/pr400011k
10.1182/blood-2016-10-743302
10.1186/1471-2148-13-121
10.1016/j.ajhg.2016.04.009
10.1084/jem.20201195
10.1172/jci.insight.121086
10.1016/j.str.2009.01.001
10.1038/ng.3569
10.3324/haematol.2018.207316
10.1186/s13062-017-0185-2
10.1212/NXG.0000000000000580
10.1016/j.cels.2015.12.004
10.1016/j.bbrc.2009.04.004
10.1002/ijc.24965
10.1038/sj.jid.5701203
10.7150/ijbs.9143
10.1016/j.ajhg.2018.01.019
10.1002/pro.703
10.1371/journal.ppat.1006884
10.1542/peds.2011-1854
10.1086/508069
10.1038/s41576-020-0255-7
10.1212/NXG.0000000000000183
10.1128/mBio.00385-13
10.1186/s12883-019-1319-1
10.7554/eLife.17755
10.3324/haematol.2017.180778
10.1016/j.ccr.2013.08.011
10.1128/JVI.02243-10
10.1038/nature03465
ContentType Journal Article
Copyright Copyright © 2021 the Author(s). Published by PNAS.
Copyright National Academy of Sciences Aug 24, 2021
Copyright © 2021 the Author(s). Published by PNAS. 2021
Copyright_xml – notice: Copyright © 2021 the Author(s). Published by PNAS.
– notice: Copyright National Academy of Sciences Aug 24, 2021
– notice: Copyright © 2021 the Author(s). Published by PNAS. 2021
DBID CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
7QG
7QL
7QP
7QR
7SN
7SS
7T5
7TK
7TM
7TO
7U9
8FD
C1K
FR3
H94
M7N
P64
RC3
7X8
5PM
DOI 10.1073/pnas.2110190118
DatabaseName Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
CrossRef
Animal Behavior Abstracts
Bacteriology Abstracts (Microbiology B)
Calcium & Calcified Tissue Abstracts
Chemoreception Abstracts
Ecology Abstracts
Entomology Abstracts (Full archive)
Immunology Abstracts
Neurosciences Abstracts
Nucleic Acids Abstracts
Oncogenes and Growth Factors Abstracts
Virology and AIDS Abstracts
Technology Research Database
Environmental Sciences and Pollution Management
Engineering Research Database
AIDS and Cancer Research Abstracts
Algology Mycology and Protozoology Abstracts (Microbiology C)
Biotechnology and BioEngineering Abstracts
Genetics Abstracts
MEDLINE - Academic
PubMed Central (Full Participant titles)
DatabaseTitle MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
CrossRef
Virology and AIDS Abstracts
Oncogenes and Growth Factors Abstracts
Technology Research Database
Nucleic Acids Abstracts
Ecology Abstracts
Neurosciences Abstracts
Biotechnology and BioEngineering Abstracts
Environmental Sciences and Pollution Management
Entomology Abstracts
Genetics Abstracts
Animal Behavior Abstracts
Bacteriology Abstracts (Microbiology B)
Algology Mycology and Protozoology Abstracts (Microbiology C)
AIDS and Cancer Research Abstracts
Chemoreception Abstracts
Immunology Abstracts
Engineering Research Database
Calcium & Calcified Tissue Abstracts
MEDLINE - Academic
DatabaseTitleList CrossRef

Virology and AIDS Abstracts

MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Sciences (General)
EISSN 1091-6490
EndPage 11
ExternalDocumentID 10_1073_pnas_2110190118
34417303
27075533
Genre Journal Article
Case Reports
GrantInformation_xml – fundername: Department of Health | National Health and Medical Research Council (NHMRC)
  grantid: APP1108800
– fundername: Department of Health | National Health and Medical Research Council (NHMRC)
  grantid: APP1081858
– fundername: Department of Health | National Health and Medical Research Council (NHMRC)
  grantid: APP1113904
GroupedDBID ---
-DZ
-~X
.55
0R~
123
29P
2AX
2FS
2WC
4.4
53G
5RE
5VS
85S
AACGO
AAFWJ
AANCE
ABBHK
ABOCM
ABPLY
ABPPZ
ABTLG
ABXSQ
ABZEH
ACGOD
ACIWK
ACNCT
ACPRK
ADACV
AENEX
AEUPB
AEXZC
AFFNX
AFOSN
AFRAH
ALMA_UNASSIGNED_HOLDINGS
BKOMP
CS3
D0L
DCCCD
DIK
DU5
E3Z
EBS
F5P
FRP
GX1
H13
HH5
HYE
IPSME
JAAYA
JBMMH
JENOY
JHFFW
JKQEH
JLS
JLXEF
JPM
JSG
JST
KQ8
L7B
LU7
N9A
N~3
O9-
OK1
PNE
PQQKQ
R.V
RHF
RHI
RNA
RNS
RPM
RXW
SA0
SJN
TAE
TN5
UKR
VQA
W8F
WH7
WOQ
WOW
X7M
XSW
Y6R
YBH
YKV
YSK
ZCA
~02
~KM
CGR
CUY
CVF
ECM
EIF
NPM
AAYXX
CITATION
7QG
7QL
7QP
7QR
7SN
7SS
7T5
7TK
7TM
7TO
7U9
8FD
C1K
FR3
H94
M7N
P64
RC3
7X8
5PM
ID FETCH-LOGICAL-c4248-60eda478c5ccbd409d50184fe7342c6aded12417cbf15358f5955b50bc6688bb3
IEDL.DBID RPM
ISSN 0027-8424
IngestDate Tue Sep 17 21:16:40 EDT 2024
Tue Aug 27 04:49:56 EDT 2024
Mon Dec 16 18:29:43 EST 2024
Fri Dec 06 02:30:46 EST 2024
Sat Sep 28 08:30:37 EDT 2024
Tue Dec 10 23:16:26 EST 2024
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 34
Keywords pathogen-associated molecular pattern receptor
translational repression
nucleotide-binding and oligomerization domain
autoinflammatory disease
virus sensing
Language English
License Copyright © 2021 the Author(s). Published by PNAS.
This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c4248-60eda478c5ccbd409d50184fe7342c6aded12417cbf15358f5955b50bc6688bb3
Notes ObjectType-Case Study-2
SourceType-Scholarly Journals-1
ObjectType-Feature-4
content type line 23
ObjectType-Report-1
ObjectType-Article-3
Reviewers: A.F., Institut Imagine des Maladies Génétiques; and B.M., National Institute of Allergy and Infectious Diseases, NIH.
Contributed by Christopher C. Goodnow, July 11, 2021 (sent for review June 16, 2021; reviewed by Alain Fischer and Bernard Moss)
Author contributions: A.J.R., P.E.G., and C.C.G. designed research; A.J.R., P.E.G., J.B.Z., Y.J.K., S.S., and W.A.S. performed research; A.J.R., P.E.G., J.B.Z., Y.J.K., S.S., W.A.S., and C.C.G. analyzed data; and A.J.R., P.E.G., and C.C.G. wrote the paper.
ORCID 0000-0001-5296-6155
OpenAccessLink https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403910/
PMID 34417303
PQID 2565687964
PQPubID 42026
PageCount 11
ParticipantIDs pubmedcentral_primary_oai_pubmedcentral_nih_gov_8403910
proquest_miscellaneous_2563420455
proquest_journals_2565687964
crossref_primary_10_1073_pnas_2110190118
pubmed_primary_34417303
jstor_primary_27075533
PublicationCentury 2000
PublicationDate 2021-08-24
PublicationDateYYYYMMDD 2021-08-24
PublicationDate_xml – month: 08
  year: 2021
  text: 2021-08-24
  day: 24
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
– name: Washington
PublicationTitle Proceedings of the National Academy of Sciences - PNAS
PublicationTitleAlternate Proc Natl Acad Sci U S A
PublicationYear 2021
Publisher National Academy of Sciences
Publisher_xml – sequence: 0
  name: National Academy of Sciences
– name: National Academy of Sciences
References e_1_3_3_17_2
e_1_3_3_16_2
e_1_3_3_19_2
e_1_3_3_18_2
e_1_3_3_13_2
e_1_3_3_36_2
e_1_3_3_12_2
e_1_3_3_37_2
e_1_3_3_15_2
e_1_3_3_34_2
e_1_3_3_14_2
e_1_3_3_35_2
e_1_3_3_32_2
e_1_3_3_33_2
e_1_3_3_11_2
e_1_3_3_30_2
e_1_3_3_10_2
e_1_3_3_31_2
e_1_3_3_6_2
e_1_3_3_5_2
e_1_3_3_8_2
e_1_3_3_7_2
e_1_3_3_28_2
e_1_3_3_9_2
e_1_3_3_27_2
e_1_3_3_29_2
e_1_3_3_24_2
e_1_3_3_23_2
e_1_3_3_26_2
e_1_3_3_25_2
e_1_3_3_2_2
e_1_3_3_20_2
e_1_3_3_1_2
e_1_3_3_4_2
e_1_3_3_22_2
e_1_3_3_3_2
e_1_3_3_21_2
References_xml – ident: e_1_3_3_6_2
  doi: 10.1128/JVI.01329-18
– ident: e_1_3_3_29_2
  doi: 10.1111/jns.12409
– ident: e_1_3_3_33_2
  doi: 10.1093/nar/gkt473
– ident: e_1_3_3_31_2
  doi: 10.1038/nmeth.1314
– ident: e_1_3_3_17_2
  doi: 10.1172/JCI129301
– ident: e_1_3_3_4_2
  doi: 10.1128/mBio.01122-15
– ident: e_1_3_3_5_2
  doi: 10.1128/JVI.02262-14
– ident: e_1_3_3_9_2
  doi: 10.1021/pr400011k
– ident: e_1_3_3_16_2
  doi: 10.1182/blood-2016-10-743302
– ident: e_1_3_3_1_2
  doi: 10.1186/1471-2148-13-121
– ident: e_1_3_3_22_2
  doi: 10.1016/j.ajhg.2016.04.009
– ident: e_1_3_3_32_2
  doi: 10.1084/jem.20201195
– ident: e_1_3_3_37_2
  doi: 10.1172/jci.insight.121086
– ident: e_1_3_3_12_2
  doi: 10.1016/j.str.2009.01.001
– ident: e_1_3_3_23_2
  doi: 10.1038/ng.3569
– ident: e_1_3_3_36_2
  doi: 10.3324/haematol.2018.207316
– ident: e_1_3_3_11_2
  doi: 10.1186/s13062-017-0185-2
– ident: e_1_3_3_30_2
  doi: 10.1212/NXG.0000000000000580
– ident: e_1_3_3_13_2
  doi: 10.1016/j.cels.2015.12.004
– ident: e_1_3_3_21_2
  doi: 10.1016/j.bbrc.2009.04.004
– ident: e_1_3_3_3_2
  doi: 10.1002/ijc.24965
– ident: e_1_3_3_19_2
  doi: 10.1038/sj.jid.5701203
– ident: e_1_3_3_10_2
  doi: 10.7150/ijbs.9143
– ident: e_1_3_3_35_2
  doi: 10.1016/j.ajhg.2018.01.019
– ident: e_1_3_3_14_2
  doi: 10.1002/pro.703
– ident: e_1_3_3_2_2
  doi: 10.1371/journal.ppat.1006884
– ident: e_1_3_3_26_2
  doi: 10.1542/peds.2011-1854
– ident: e_1_3_3_20_2
  doi: 10.1086/508069
– ident: e_1_3_3_18_2
  doi: 10.1038/s41576-020-0255-7
– ident: e_1_3_3_25_2
  doi: 10.1212/NXG.0000000000000183
– ident: e_1_3_3_7_2
  doi: 10.1128/mBio.00385-13
– ident: e_1_3_3_34_2
  doi: 10.1186/s12883-019-1319-1
– ident: e_1_3_3_28_2
  doi: 10.7554/eLife.17755
– ident: e_1_3_3_24_2
  doi: 10.3324/haematol.2017.180778
– ident: e_1_3_3_15_2
  doi: 10.1016/j.ccr.2013.08.011
– ident: e_1_3_3_8_2
  doi: 10.1128/JVI.02243-10
– ident: e_1_3_3_27_2
  doi: 10.1038/nature03465
SSID ssj0009580
Score 2.4862614
Snippet 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...
The experiments here advance understanding of the function of the SAMD9L gene and protein in innate immune mechanisms in resisting virus infection and in the...
SourceID pubmedcentral
proquest
crossref
pubmed
jstor
SourceType Open Access Repository
Aggregation Database
Index Database
Publisher
StartPage 1
SubjectTerms Amino acids
Anemia
Ataxia
Ataxia - genetics
Ataxia - pathology
Basal ganglia
Biological Sciences
Child
Children
Female
Fluorescence
Frameshift mutation
Fusion protein
Ganglia
Gene Expression Regulation
Gene sequencing
Genomes
Green fluorescent protein
Heterozygote
Homology
Humans
Infant, Newborn
Inflammation
Inflammatory diseases
Interferon
Lymphocytes B
Male
mRNA
Mutation
Mutation, Missense
Myelodysplastic Syndromes - genetics
Myelodysplastic Syndromes - pathology
Neonates
Neutrophilia
Nucleotides
Oligomerization
Pancytopenia
Pancytopenia - genetics
Pancytopenia - pathology
Protein Biosynthesis
Proteins
Red fluorescent protein
Thrombocytopenia
Translation
Tumor Suppressor Proteins - genetics
Viruses
Whole genome sequencing
Title SAMD9L autoinflammatory or ataxia pancytopenia disease mutations activate cell-autonomous translational repression
URI https://www.jstor.org/stable/27075533
https://www.ncbi.nlm.nih.gov/pubmed/34417303
https://www.proquest.com/docview/2565687964
https://search.proquest.com/docview/2563420455
https://pubmed.ncbi.nlm.nih.gov/PMC8403910
Volume 118
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwEB61PaBeEAUKKaUyEodyyG42tuPkWBWqCrEICSr1FtmOLVbqZle7WdSf3xnHCRRx4hjFtpKZ8cxnzwvgvde5cHrG06YoZSq8sWlpeZUq3ajMF5nyIcN7_rW4vhGfb-XtHsghFyYE7VuzmLR3y0m7-BliK9dLOx3ixKbf5pd4KOFo5qb7sI_mdziij5V2yz7vJEf1K3Ix1PNRfLpu9XZCJ55ZSLg8hCecOnDxoWNWtEp9YOK_IOffkZN_mKKrZ_A0Ykh20X_rEey59jkcxV26ZeexlPSHF7D5fjH_WH1hetetUJSQ-8vgVWerDdOdvl9otib12lETLXyI7hq23PUe-i2jvIdfiEcZ3fCntE67otsC1pGRu4tXiWwzBNS2L-Hm6tOPy-s0dllILVKnTIvMNVqo0kprTYPHvYZq_AnvFBe5LXTjGsQAM2WNR-0oSy8rKY3MjC2KsjSGH8NBu2rda2AKye-F8k4LI5yYGQqf85VHWOErLlUC5wOV63VfTKMOTnDFa-JN_Zs3CRwHLozjcoXgBrFpAqcDW-q43XAewdKSsmoTeDe-xo1CtNGtQ7LQGPwhRLAygVc9F8fFBzFIQD3i7ziAinA_foOyGYpxR1k8-e-Zb-AwpziZDDWWOIWDbrNzbxHodOaMzIw8C-L9AOx4_60
link.rule.ids 230,314,727,780,784,885,27924,27925,53791,53793
linkProvider National Library of Medicine
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3db9MwED-NIcFeEAO2BcYwEg_jIW0S23HyOI1NBdoJiU3aW2Q7tlZpdas2Rfz5nJ0PGOKJxyi2ldyd7372fQF8sDJjRqY0rvOCx8wqHRealrGQtUhsnggbMrxnV_nkhn255bc7wPtcmBC0r9V85O4XIze_C7GVq4Ue93Fi42-zczyUUDRz40fwmFNRpv0hfai1W7SZJxkqYJaxvqKPoOOVk5uRP_OkIeVyD55Q34OL9j2zOrvUhib-C3T-HTv5hzG6fA7POhRJztqv3Ycd417AfrdPN-S0Kyb98SWsv5_NPpVTIrfNEoUJ-b8IfnWyXBPZyJ9zSVZewTa-jRY-dA4bsti2PvoN8ZkPPxCREn_HH_t13NLfF5DGm7n77jKRrPuQWvcKbi4vrs8ncddnIdZInSLOE1NLJgrNtVY1HvhqX-WPWSMoy3Qua1MjCkiFVhb1Iy8sLzlXPFE6z4tCKXoAu27pzBEQgeS3TFgjmWKGpcoH0NnSIrCwJeUigtOeytWqLadRBTe4oJXnTfWbNxEcBC4M4zKB8AbRaQTHPVuqbsPhPA9MC59XG8H74TVuFU8b6QySxY_BH0IMyyM4bLk4LN6LQQTiAX-HAb4M98M3KJ2hHHcnja__e-Y7eDq5nk2r6eerr29gL_NRMwnqL3YMu816a94i7GnUSRDyX3vhAis
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9QwEB5BkapeEAUKgQJG4lAO2WRjO06OVcuqQLeqBJV6i2zHFit1s9FuturPZ-w4oUWcOEaxrWRmPPPZ8wL4ZGXGjJzSuM4LHjOrdFxoWsZC1iK1eSqsz_CeX-RnV-zbNb--1-rLB-1rtZg0N8tJs_jlYyvbpU6GOLHkcn6ChxKKZi5pa5s8hiecopANB_Wx3m7RZ59kqIRZxoaqPoImbSM3E3fumfq0yz3Ypa4PFx36ZgXb1Icn_gt4_h0_ec8gzZ7B04AkyXH_xfvwyDTPYT_s1Q05CgWlP7-A9Y_j-Wl5TuS2W6FAoQwsvW-drNZEdvJuIUnrlGznWmnhQ3DakOW299NviMt-uEVUStw9f-zWaVbuzoB0ztTdhAtFsh7CapuXcDX78vPkLA69FmKN1CniPDW1ZKLQXGtV46GvdpX-mDWCskznsjY1IoGp0MqijuSF5SXniqdK53lRKEUPYKdZNeY1EIHkt0xYI5lihk2VC6KzpUVwYUvKRQRHA5Wrti-pUXlXuKCV4031hzcRHHgujOMygRAHEWoEhwNbqrDpcJ4Dp4XLrY3g4_gat4ujjWwMksWNwR9CHMsjeNVzcVx8EIMIxAP-jgNcKe6Hb1BCfUnuIJFv_nvmB9i9PJ1V518vvr-FvcwFzqSowtgh7HTrrXmHyKdT772M_wYtqwM-
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=SAMD9L+autoinflammatory+or+ataxia+pancytopenia+disease+mutations+activate+cell-autonomous+translational+repression&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+-+PNAS&rft.au=Russell%2C+Amanda+J&rft.au=Gray%2C+Paul+E&rft.au=Ziegler%2C+John+B&rft.au=Kim%2C+Yae+Jean&rft.date=2021-08-24&rft.pub=National+Academy+of+Sciences&rft.issn=0027-8424&rft.eissn=1091-6490&rft.volume=118&rft.issue=34&rft.spage=1&rft_id=info:doi/10.1073%2Fpnas.2110190118&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0027-8424&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0027-8424&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0027-8424&client=summon