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Article Dans Une Revue Blood Année : 2019

EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome

Shengjiang Tan
  • Fonction : Auteur
Angela Hoslin
  • Fonction : Auteur
Pekka Jaako
  • Fonction : Auteur
Abraham Acevedo-Arozena
  • Fonction : Auteur
Stefano Fumagalli
  • Fonction : Auteur
Blandine Beaupain
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  • PersonId : 937574
Alan Warren

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 EFL1 mutations in SDS, we define this leukemia predisposition disorder as a ribosomopathy that is caused by corruption of a fundamental, conserved mechanism, which licenses entry of the large ribosomal subunit into translation.

Dates et versions

hal-02347758 , version 1 (05-11-2019)

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Shengjiang Tan, Laetitia Kermasson, Angela Hoslin, Pekka Jaako, Alexandre Faille, et al.. EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome. Blood, 2019, 134 (3), pp.277-290. ⟨10.1182/blood.2018893404⟩. ⟨hal-02347758⟩
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