title: The Musashi 1 Controls the Splicing of Photoreceptor-Specific Exons in the Vertebrate Retina.
abstract: Alternative pre-mRNA splicing expands the coding capacity of eukaryotic genomes, potentially enabling a limited number of genes to govern the development of complex anatomical structures. Alternative splicing is particularly prevalent in the vertebrate nervous system, where it is required for neuronal development and function. Here, we show that photoreceptor cells, a type of sensory neuron, express a characteristic splicing program that affects a broad set of transcripts and is initiated prior to the development of the light sensing outer segments. Surprisingly, photoreceptors lack prototypical neuronal splicing factors and their splicing profile is driven to a significant degree by the Musashi 1 (MSI1) protein. A striking feature of the photoreceptor splicing program are exons that display a "switch-like" pattern of high inclusion levels in photoreceptors and near complete exclusion outside of the retina. Several ubiquitously expressed genes that are involved in the biogenesis and function of primary cilia produce highly photoreceptor specific isoforms through use of such "switch-like" exons. Our results suggest a potential role for alternative splicing in the development of photoreceptors and the conversion of their primary cilia to the light sensing outer segments.
authors.affiliation: Department of Biochemistry, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Murphy
authors.affiliation: Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Benjamin
authors.identifier: 0000-0002-9281-2289
authors.initials: B
authors.lastname: Cieply
authors.affiliation: Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Russ
authors.initials: R
authors.lastname: Carstens
authors.affiliation: Departments of Biochemistry, Ophthalmology and Center for Neuroscience, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia, United States of America.
authors.forename: Visvanathan
authors.identifier: 0000-0003-0289-3685
authors.initials: V
authors.lastname: Ramamurthy
authors.affiliation: Department of Biochemistry and Cancer Institute, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia, United States of America.
authors.forename: Peter
authors.identifier: 0000-0003-1108-7271
authors.initials: P
authors.lastname: Stoilov
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D005091:Exons / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D010786:Photoreceptor Cells / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D012160:Retina / Q000254:growth & development / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism; D014714:Vertebrates / Q000235:genetics / Q000254:growth & development
chemical_list: C104786:Msi1h protein, mouse; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins