RRC ID 12041
Author Underwood JG, Boutz PL, Dougherty JD, Stoilov P, Black DL.
Title Homologues of the Caenorhabditis elegans Fox-1 protein are neuronal splicing regulators in mammals.
Journal Mol. Cell. Biol.
Abstract A vertebrate homologue of the Fox-1 protein from C. elegans was recently shown to bind to the element GCAUG and to act as an inhibitor of alternative splicing patterns in muscle. The element UGCAUG is a splicing enhancer element found downstream of numerous neuron-specific exons. We show here that mouse Fox-1 (mFox-1) and another homologue, Fox-2, are both specifically expressed in neurons in addition to muscle and heart. The mammalian Fox genes are very complex transcription units that generate transcripts from multiple promoters and with multiple internal exons whose inclusion is regulated. These genes produce a large family of proteins with variable N and C termini and internal deletions. We show that the overexpression of both Fox-1 and Fox-2 isoforms specifically activates splicing of neuronally regulated exons. This splicing activation requires UGCAUG enhancer elements. Conversely, RNA interference-mediated knockdown of Fox protein expression inhibits splicing of UGCAUG-dependent exons. These experiments show that this large family of proteins regulates splicing in the nervous system. They do this through a splicing enhancer function, in addition to their apparent negative effects on splicing in vertebrate muscle and in worms.
Volume 25(22)
Pages 10005-16
Published 2005-11
DOI 10.1128/MCB.25.22.10005-10016.2005
PII 25/22/10005
PMID 16260614
PMC PMC1280273
MeSH Animals Blotting, Northern Blotting, Western Brain / metabolism Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Carrier Proteins / genetics Carrier Proteins / physiology* Cross-Linking Reagents / pharmacology Enhancer Elements, Genetic Exons Fibronectins / metabolism Gene Expression Regulation HeLa Cells Hippocampus / metabolism Humans Immunohistochemistry Introns Mice Models, Genetic Muscles / metabolism Neurons / metabolism* Plasmids / metabolism Promoter Regions, Genetic Protein Binding Protein Isoforms Protein Structure, Tertiary RNA Interference RNA Splicing* RNA Splicing Factors RNA, Messenger / metabolism RNA, Small Interfering / metabolism RNA-Binding Proteins / genetics RNA-Binding Proteins / physiology* Repressor Proteins / genetics Repressor Proteins / physiology* Reverse Transcriptase Polymerase Chain Reaction Tissue Distribution Transfection
IF 3.735
Times Cited 165
DNA material cDNA library of mixed-stage C. elegans for yeast two-hybrid screening (RDB1864)