title: Isoform-specific proteasomal degradation of Rbfox3 during chicken embryonic development.
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.
authors.affiliation: Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Kee K
authors.initials: KK
authors.lastname: Kim
authors.affiliation: Laboratory of Molecular Cardiology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Adelstein
authors.affiliation: 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.
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Kawamoto
mesh_terms: D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D017931:DNA Primers; D007527:Isoenzymes / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D046988:Proteasome Endopeptidase Complex
keywords: Alternative splicing; Neural development; Proteasome degradation; RNA recognition motif; Rbfox family; Rbfox3