PUBLICATION

Altered RNA metabolism due to a homozygous RBM7 mutation in a patient with spinal motor neuropathy

Authors
Giunta, M., Edvardson, S., Xu, Y., Schuelke, M., Gomez-Duran, A., Boczonadi, V., Elpeleg, O., Müller, J.S., Horvath, R.
ID
ZDB-PUB-160520-7
Date
2016
Source
Human molecular genetics   25(14): 2985-2996 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Animals
  • Cerebellum/metabolism
  • Cerebellum/pathology
  • Disease Models, Animal
  • Exosome Multienzyme Ribonuclease Complex/genetics*
  • Exosomes/genetics
  • Humans
  • Motor Neurons/metabolism
  • Motor Neurons/pathology
  • Muscular Atrophy, Spinal/genetics*
  • Muscular Atrophy, Spinal/metabolism
  • Muscular Atrophy, Spinal/pathology
  • Mutation
  • RNA-Binding Proteins/genetics*
  • Sequence Analysis, RNA
  • Zebrafish/metabolism
PubMed
27193168 Full text @ Hum. Mol. Genet.
Abstract
The exosome complex is the most important RNA processing machinery within the cell. Mutations in its subunits EXOSC8 and EXOSC3 cause pontocerebellar hypoplasia, spinal muscular atrophy (SMA) and central nervous system demyelination. We present a patient with SMA-like phenotype carrying a homozygous mutation in RBM7 - a subunit of the nuclear exosome targeting (NEXT) complex - which is known to bind and carry specific subtypes of coding and non-coding RNAs to the exosome. The NEXT complex with other protein complexes is responsible for the substrate specificity of the exosome. We performed RNA-sequencing (RNA-seq) analysis on primary fibroblasts of patients with mutations in EXOSC8 and RBM7 and gene knock-down experiments using zebrafish as a model system. RNA-seq analysis identified significantly altered expression of 62 transcripts shared by the two patient cell lines. Knock-down of rbm7, exosc8 and exosc3 in zebrafish showed a common pattern of defects in motor neurons and cerebellum. Our data indicate that impaired RNA metabolism may underlie the clinical phenotype by fine tuning gene expression which is essential for correct neuronal differentiation.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes