EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome.
Adolescent
Animals
Cells, Cultured
DNA Mutational Analysis
Disease Models, Animal
Disease Susceptibility
Female
Genome-Wide Association Study
Humans
Infant
Male
Mice
Mice, Transgenic
Models, Molecular
Mutation
Pedigree
Peptide Elongation Factors
/ chemistry
Peptide Initiation Factors
/ biosynthesis
Phenotype
Protein Conformation
Ribonucleoprotein, U5 Small Nuclear
/ chemistry
Shwachman-Diamond Syndrome
/ diagnosis
Structure-Activity Relationship
Whole Genome Sequencing
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
18 07 2019
18 07 2019
Historique:
received:
21
12
2018
accepted:
10
05
2019
pubmed:
4
6
2019
medline:
15
1
2020
entrez:
2
6
2019
Statut:
ppublish
Résumé
Shwachman-Diamond syndrome (SDS) is a recessive disorder typified by bone marrow failure and predisposition to hematological malignancies. SDS is predominantly caused by deficiency of the allosteric regulator Shwachman-Bodian-Diamond syndrome that cooperates with elongation factor-like GTPase 1 (EFL1) to catalyze release of the ribosome antiassociation factor eIF6 and activate translation. Here, we report biallelic mutations in EFL1 in 3 unrelated individuals with clinical features of SDS. Cellular defects in these individuals include impaired ribosomal subunit joining and attenuated global protein translation as a consequence of defective eIF6 eviction. In mice, Efl1 deficiency recapitulates key aspects of the SDS phenotype. By identifying biallelic
Identifiants
pubmed: 31151987
pii: S0006-4971(20)42400-0
doi: 10.1182/blood.2018893404
pmc: PMC6754720
doi:
Substances chimiques
EFL1 protein, human
0
Peptide Elongation Factors
0
Peptide Initiation Factors
0
Ribonucleoprotein, U5 Small Nuclear
0
eIF-6
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
277-290Subventions
Organisme : Medical Research Council
ID : MC_PC_12009
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UP_A390_1106
Pays : United Kingdom
Organisme : Medical Research Council
ID : 1330931
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L003368/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U105161083
Pays : United Kingdom
Informations de copyright
© 2019 by The American Society of Hematology.
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