Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability.
BMC Med Genomics
; 11(1): 41, 2018 04 23.
Article
in En
| MEDLINE
| ID: mdl-29685133
ABSTRACT
BACKGROUND:
Decapping of mRNA is an important step in the regulation of mRNA turnover and therefore of gene expression, which is a key process controlling development and homeostasis of all organisms. It has been shown that EDC3 plays a role in mRNA decapping, however its function is not well understood. Previously, we have associated a homozygous variant in EDC3 with autosomal recessive intellectual disability. Here, we investigate the functional role of EDC3.METHODS:
We performed transcriptome analyses in patients' samples. In addition, we established an EDC3 loss-of-function model using siRNA-based knockdown in the human neuroblastoma cell line SKNBE and carried out RNA sequencing. Integrative bioinformatics analyses were performed to identify EDC3-dependent candidate genes and/or pathways.RESULTS:
Our analyses revealed that 235 genes were differentially expressed in patients versus controls. In addition, AU-rich element (ARE)-containing mRNAs, whose degradation in humans has been suggested to involve EDC3, had higher fold changes than non-ARE-containing genes. The analysis of RNA sequencing data from the EDC3 in vitro loss-of-function model confirmed the higher fold changes of ARE-containing mRNAs compared to non-ARE-containing mRNAs and further showed an upregulation of long non-coding and coding RNAs. In total, 764 genes were differentially expressed. Integrative bioinformatics analyses of these genes identified dysregulated candidate pathways, including pathways related to synapses/coated vesicles and DNA replication/cell cycle.CONCLUSION:
Our data support the involvement of EDC3 in mRNA decay, including ARE-containing mRNAs, and suggest that EDC3 might be preferentially involved in the degradation of long coding and non-coding RNAs. Furthermore, our results associate ECD3 loss-of-function with synapses-related pathways. Collectively, our data provide novel information that might help elucidate the molecular mechanisms underlying the association of intellectual disability with the dysregulation of mRNA degradation.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ribonucleoproteins, Small Nuclear
/
Computational Biology
/
RNA Stability
/
Intellectual Disability
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
BMC Med Genomics
Journal subject:
GENETICA MEDICA
Year:
2018
Document type:
Article
Affiliation country:
Germany