PUBLICATION

In vivo mutation of pre-mRNA processing factor 8 (Prpf8) affects transcript splicing, cell survival and myeloid differentiation

Authors
Keightley, M.C., Crowhurst, M.O., Layton, J.E., Beilharz, T., Markmiller, S., Varma, S., Hogan, B.M., de Jong-Curtain, T.A., Heath, J.K., and Lieschke, G.J.
ID
ZDB-PUB-130708-8
Date
2013
Source
FEBS letters   587(14): 2150-2157 (Journal)
Registered Authors
Crowhurst, Meredith, de Jong-Curtain, Tanya A., Heath, Joan K., Hogan, Ben M., Keightley, M. Cristina, Layton, Judy E., Lieschke, Graham J., Markmiller, Sebastian, Varma, Sony
Keywords
PRPF8, haematopoiesis, splicing, zebrafish, myelopoiesis, spliceosome, snRNP
MeSH Terms
  • Ribonucleoproteins, Small Nuclear/genetics
  • Ribonucleoproteins, Small Nuclear/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • RNA Splicing*
  • Zebrafish
  • Animals
  • Embryo, Nonmammalian/abnormalities
  • Embryo, Nonmammalian/pathology
  • Humans
  • Myeloid Cells/physiology*
  • Cell Survival
  • Codon, Nonsense*
  • RNA-Binding Proteins/genetics*
  • RNA-Binding Proteins/metabolism
  • Base Sequence
  • Genes, Lethal
  • Body Patterning/genetics
  • Sequence Analysis, DNA
  • Cell Differentiation*
  • RNA Precursors/genetics
  • RNA Precursors/metabolism
PubMed
23714367 Full text @ FEBS Lett.
Abstract

Mutated spliceosome components are recurrently being associated with perturbed tissue development and disease pathogenesis. CephalophOnus (cph), is a zebrafish mutant carrying an early premature STOP codon in the spliceosome component Prpf8 (pre-mRNA processing factor 8). Cph initially develops normally, but then develops widespread cell death, especially in neurons, and is embryonic lethal. Cph mutants accumulate aberrantly spliced transcripts retaining both U2- and U12-type introns. Within early haematopoiesis, myeloid differentiation is impaired, suggesting Prpf8 is required for haematopoietic development. Cph provides an animal model for zygotic PRPF8 dysfunction diseases and for evaluating therapeutic interventions.

Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping