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


ABSTRACT: Mutated spliceosome components are recurrently being associated with perturbed tissue development and disease pathogenesis. Cephalopho?nus (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.

SUBMITTER: Keightley MC 

PROVIDER: S-EPMC3820954 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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

Keightley Maria-Cristina MC   Crowhurst Meredith O MO   Layton Judith E JE   Beilharz Traude T   Markmiller Sebastian S   Varma Sony S   Hogan Benjamin M BM   de Jong-Curtain Tanya A TA   Heath Joan K JK   Lieschke Graham J GJ  

FEBS letters 20130525 14


Mutated spliceosome components are recurrently being associated with perturbed tissue development and disease pathogenesis. Cephalophŏnus (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 ear  ...[more]

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