Loss of the Scavenger mRNA Decapping Enzyme DCPS Causes Syndromic Intellectual Disability with Neuromuscular Defects.
Fiche publication
Date publication
février 2015
Auteurs
Membres identifiés du Cancéropôle Est :
Dr SERAPHIN Bertrand
Tous les auteurs :
Ng C, Shboul M, Taverniti V, Bonnard C, Lee H, Eskin A, Nelson SF, Al-Raqad M, Altawalbeh S, Seraphin B, Reversade B
Lien Pubmed
Résumé
mRNA decay is an essential and active process that allows cells to continuously adapt gene expression to internal and environmental cues. There are two mRNA degradation pathways: 3' to 5' and 5' to 3'. The DCPS protein is the scavenger mRNA decapping enzyme which functions in the last step of the 3' end mRNA decay pathway. We have identified a DCPS pathogenic mutation in a large family with three affected individuals presenting with a novel recessive syndrome consisting of craniofacial anomalies, intellectual disability and neuromuscular defects. Using patient's primary cells, we show that this homozygous splice mutation results in a DCPS loss-of-function allele. Diagnostic biochemical analyses using various m7G cap derivatives as substrates reveal no DCPS enzymatic activity in patient's cells. Our results implicate DCPS and more generally RNA catabolism, as a critical cellular process for neurological development, normal cognition and organismal homeostasis in humans.
Référence
Hum Mol Genet. 2015 Feb 24. pii: ddv067.