Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P04637 (
p53
)
77,613
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The RNA exosome is a ubiquitously expressed complex of nine core proteins (
EXOSC1
-9) and associated nucleases responsible for RNA processing and degradation. Mutations in
EXOSC3
,
EXOSC8
,
EXOSC9
, and the exosome cofactor
RBM7
cause pontocerebellar hypoplasia and motor neuronopathy. We investigated the consequences of exosome mutations on RNA metabolism and cellular survival in zebrafish and human cell models. We observed that levels of mRNAs encoding
p53
and ribosome biogenesis factors are increased in zebrafish lines with homozygous mutations of
exosc8
or
exosc9
, respectively. Consistent with higher
p53
levels, mutant zebrafish have a reduced head size, smaller brain, and cerebellum caused by an increased number of apoptotic cells during development. Down-regulation of
EXOSC8
and
EXOSC9
in human cells leads to
p53 protein
stabilisation and G2/M cell cycle arrest. Increased
p53
transcript levels were also observed in muscle samples from patients with
EXOSC9
mutations. Our work provides explanation for the pathogenesis of exosome-related disorders and highlights the link between exosome function, ribosome biogenesis, and
p53
-dependent signalling. We suggest that exosome-related disorders could be classified as ribosomopathies.
...
PMID:RNA exosome mutations in pontocerebellar hypoplasia alter ribosome biogenesis and p53 levels. 3252 37
