EFL1 mutations impair eIF6 release to cause Shwachman-Diamond syndrome
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.
Source: Blood - Category: Hematology Authors: Tan, S., Kermasson, L., Hoslin, A., Jaako, P., Faille, A., Acevedo-Arozena, A., Lengline, E., Ranta, D., Poiree, M., Fenneteau, O., Ducou le Pointe, H., Fumagalli, S., Beaupain, B., Nitschke, P., Bole-Feysot, C., de Villartay, J.-P., Bellanne-Chantelot, C Tags: Hematopoiesis and Stem Cells, Myeloid Neoplasia, Red Cells, Iron, and Erythropoiesis Source Type: research