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Biochem Biophys Res Commun. 2014 Aug 8;450(4):1662-7. doi: 10.1016/j.bbrc.2014.07.057. Epub 2014 Jul 17.

Isoform-specific proteasomal degradation of Rbfox3 during chicken embryonic development.

Author information

1
Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States.
2
Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States. Electronic address: kawamots@mail.nih.gov.

Abstract

Rbfox3, a neuron-specific RNA-binding protein, plays an important role in neuronal differentiation during development. An isoform Rbfox3-d31, which excludes the 93-nucleotide cassette exon within the RNA recognition motif of chicken Rbfox3, has been previously identified. However, the cellular functions of Rbfox3-d31 remain largely unknown. Here we find that Rbfox3-d31 mRNA is highly expressed during the early developmental stages of the chicken embryo, while Rbfox3-d31 protein is barely detected during the same stage due to its rapid degradation mediated by the ubiquitin-proteasome pathway. Importantly, this degradation is specific to the Rbfox3-d31 isoform and it does not occur with full-length Rbfox3. Furthermore, suppression of Rbfox3-d31 protein degradation with the proteasome inhibitor MG132 attenuates the splicing activity of another Rbfox family member Rbfox2 by altering the subcellular localization of Rbfox2. These results suggest that Rbfox3-d31 functions as a repressor for the splicing activity of the Rbfox family and its protein level is regulated in an isoform-specific manner in vivo.

KEYWORDS:

Alternative splicing; Neural development; Proteasome degradation; RNA recognition motif; Rbfox family; Rbfox3

PMID:
25044120
PMCID:
PMC4143327
DOI:
10.1016/j.bbrc.2014.07.057
[Indexed for MEDLINE]
Free PMC Article

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