Loss of the scavenger mRNA decapping enzyme DCPS causes syndromic intellectual disability with neuromuscular defects - Archive ouverte HAL Access content directly
Journal Articles Human Molecular Genetics Year : 2015

Loss of the scavenger mRNA decapping enzyme DCPS causes syndromic intellectual disability with neuromuscular defects

C Ng
  • Function : Author
M Shboul
  • Function : Author
Valerio Taverniti
  • Function : Author
  • PersonId : 1050463
C Bonnard
  • Function : Author
H Lee
  • Function : Author
A Eskin
  • Function : Author
S Nelson
  • Function : Author
M Al-Raqad
  • Function : Author
S Altawalbeh
  • Function : Author
B Reversade
  • Function : Author

Abstract

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.

Dates and versions

hal-02179565 , version 1 (10-07-2019)

Identifiers

Cite

C Ng, M Shboul, Valerio Taverniti, C Bonnard, H Lee, et al.. Loss of the scavenger mRNA decapping enzyme DCPS causes syndromic intellectual disability with neuromuscular defects. Human Molecular Genetics, 2015, 24 (11), pp.3163-3171. ⟨10.1093/hmg/ddv067⟩. ⟨hal-02179565⟩
13 View
0 Download

Altmetric

Share

Gmail Facebook X LinkedIn More