Specialization of the photoreceptor transcriptome by Srrm3 -dependent microexons is required for outer segment maintenance and vision.

Autor: Ciampi L; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain., Mantica F; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain., López-Blanch L; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain., Permanyer J; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain., Rodriguez-Marín C; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain., Zang J; Department of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland., Cianferoni D; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain., Jiménez-Delgado S; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain., Bonnal S; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain., Miravet-Verde S; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain., Ruprecht V; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain.; Universitat Pompeu Fabra, 08002 Barcelona, Spain., Neuhauss SCF; Department of Molecular Life Sciences, University of Zurich, CH-8057 Zurich, Switzerland., Banfi S; Medical Genetics, Department of Precision Medicine, University of Campania 'L. Vanvitelli', 80138 Naples, Italy.; Telethon Institute of Genetics and Medicine, 80078 Pozzuoli, Italy., Carrella S; Telethon Institute of Genetics and Medicine, 80078 Pozzuoli, Italy.; Ecosustainable Marine Biotechnology Department, Stazione Zoologica Anton Dohrn, 80121 Naples, Italy., Serrano L; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain.; Universitat Pompeu Fabra, 08002 Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain., Head SA; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain., Irimia M; Centre for Genomic Regulation, Barcelona Institute of Science and Technology, 08036 Barcelona, Spain.; Universitat Pompeu Fabra, 08002 Barcelona, Spain.; Institució Catalana de Recerca i Estudis Avançats, 08010 Barcelona, Spain.
Jazyk: angličtina
Zdroj: Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Jul 19; Vol. 119 (29), pp. e2117090119. Date of Electronic Publication: 2022 Jul 12.
DOI: 10.1073/pnas.2117090119
Abstrakt: Retinal photoreceptors have a distinct transcriptomic profile compared to other neuronal subtypes, likely reflecting their unique cellular morphology and function in the detection of light stimuli by way of the ciliary outer segment. We discovered a layer of this molecular specialization by revealing that the vertebrate retina expresses the largest number of tissue-enriched microexons of all tissue types. A subset of these microexons is included exclusively in photoreceptor transcripts, particularly in genes involved in cilia biogenesis and vesicle-mediated transport. This microexon program is regulated by Srrm3 , a paralog of the neural microexon regulator Srrm4 . Despite the fact that both proteins positively regulate retina microexons in vitro, only Srrm3 is highly expressed in mature photoreceptors. Its deletion in zebrafish results in widespread down-regulation of microexon inclusion from early developmental stages, followed by other transcriptomic alterations, severe photoreceptor defects, and blindness. These results shed light on the transcriptomic specialization and functionality of photoreceptors, uncovering unique cell type-specific roles for Srrm3 and microexons with implications for retinal diseases.
Databáze: MEDLINE
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