PUBLICATION

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

Authors
Ciampi, L., Mantica, F., López-Blanch, L., Permanyer, J., Rodriguez-Marín, C., Zang, J., Cianferoni, D., Jiménez-Delgado, S., Bonnal, S., Miravet-Verde, S., Ruprecht, V., Neuhauss, S.C.F., Banfi, S., Carrella, S., Serrano, L., Head, S.A., Irimia, M.
ID
ZDB-PUB-220722-6
Date
2022
Source
Proceedings of the National Academy of Sciences of the United States of America   119: e2117090119 (Journal)
Registered Authors
Irimia, Manuel, Neuhauss, Stephan, Permanyer, Jon
Keywords
alternative splicing, retinal disease model, zebrafish
Datasets
GEO:GSE180778, GEO:GSE180781
MeSH Terms
  • Animals
  • Exons
  • Gene Deletion
  • Humans
  • Proteins*/genetics
  • Proteins*/physiology
  • Retinal Photoreceptor Cell Outer Segment*/metabolism
  • Serine-Arginine Splicing Factors*/genetics
  • Serine-Arginine Splicing Factors*/physiology
  • Transcriptome
  • Vision, Ocular*/genetics
  • Vision, Ocular*/physiology
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish Proteins/genetics
PubMed
35858306 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping