Scheller U, Pfisterer K, Uebe S, Ekici AB, Reis A, Jamra R, Ferrazzi F (2018)
Publication Type: Journal article
Publication year: 2018
Book Volume: 11
Journal Issue: 1
DOI: 10.1186/s12920-018-0358-6
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.
APA:
Scheller, U., Pfisterer, K., Uebe, S., Ekici, A.B., Reis, A., Jamra, R., & Ferrazzi, F. (2018). Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability. Bmc Medical Genomics, 11(1). https://dx.doi.org/10.1186/s12920-018-0358-6
MLA:
Scheller, Ute, et al. "Integrative bioinformatics analysis characterizing the role of EDC3 in mRNA decay and its association to intellectual disability." Bmc Medical Genomics 11.1 (2018).
BibTeX: Download