title: CELF6, a member of the CELF family of RNA-binding proteins, regulates muscle-specific splicing enhancer-dependent alternative splicing.
abstract: We previously described a family of five RNA-binding proteins: CUG-binding protein, embryonic lethal abnormal vision-type RNA-binding protein 3, and the CUG-binding protein and embryonic lethal abnormal vision-type RNA-binding protein 3-like factors (CELFs) 3, 4, and 5. We demonstrated that all five of these proteins specifically activate exon inclusion of cardiac troponin T minigenes in vivo via muscle-specific splicing enhancer (MSE) sequences. We also predicted that a sixth family member, CELF6, was located on chromosome 15. Here, we describe the isolation and characterization of CELF6. Like the previously described CELF proteins, CELF6 shares a domain structure containing three RNA-binding domains and a divergent domain of unknown function. CELF6 is strongly expressed in kidney, brain, and testis and is expressed at very low levels in most other tissues. In the brain, expression is widespread and maintained from the fetus to the adult. CELF6 activates exon inclusion of a cardiac troponin T minigene in transient transfection assays in an MSE-dependent manner and can activate inclusion via multiple copies of a single element, MSE2. These results place CELF6 in a functional subfamily of CELF proteins that includes CELFs 3, 4, and 5. CELF6 also promotes skipping of exon 11 of insulin receptor, a known target of CELF activity that is expressed in kidney.
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Andrea N
authors.initials: AN
authors.lastname: Ladd
authors.forename: Nicole H
authors.initials: NH
authors.lastname: Nguyen
authors.forename: Kavin
authors.initials: K
authors.lastname: Malhotra
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Cooper
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism; D000067878:CELF Proteins; D002884:Chromosomes, Human, Pair 15; D003001:Cloning, Molecular; D003360:Cosmids / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008297:Male; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism*; D016366:Open Reading Frames; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D000067878:CELF Proteins; C486465:CELF6 protein, human; D018076:DNA, Complementary; D016601:RNA-Binding Proteins; D012313:RNA