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Proper splicing contributes to visual function in the aging Drosophila eye

Changes in splicing patterns are a characteristic of the aging transcriptome; however, it is unclear whether these age‐related changes in splicing facilitate the progressive functional decline that defines aging. In Drosophila, visual behavior declines with age and correlates with altered gene expre...

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Autores principales: Stegeman, Rachel, Hall, Hana, Escobedo, Spencer E., Chang, Henry C., Weake, Vikki M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156539/
https://www.ncbi.nlm.nih.gov/pubmed/30003673
http://dx.doi.org/10.1111/acel.12817
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author Stegeman, Rachel
Hall, Hana
Escobedo, Spencer E.
Chang, Henry C.
Weake, Vikki M.
author_facet Stegeman, Rachel
Hall, Hana
Escobedo, Spencer E.
Chang, Henry C.
Weake, Vikki M.
author_sort Stegeman, Rachel
collection PubMed
description Changes in splicing patterns are a characteristic of the aging transcriptome; however, it is unclear whether these age‐related changes in splicing facilitate the progressive functional decline that defines aging. In Drosophila, visual behavior declines with age and correlates with altered gene expression in photoreceptors, including downregulation of genes encoding splicing factors. Here, we characterized the significance of these age‐regulated splicing‐associated genes in both splicing and visual function. To do this, we identified differential splicing events in either the entire eye or photoreceptors of young and old flies. Intriguingly, aging photoreceptors show differential splicing of a large number of visual function genes. In addition, as shown previously for aging photoreceptors, aging eyes showed increased accumulation of circular RNAs, which result from noncanonical splicing events. To test whether proper splicing was necessary for visual behavior, we knocked down age‐regulated splicing factors in photoreceptors in young flies and examined phototaxis. Notably, many of the age‐regulated splicing factors tested were necessary for proper visual behavior. In addition, knockdown of individual splicing factors resulted in changes in both alternative splicing at age‐spliced genes and increased accumulation of circular RNAs. Together, these data suggest that cumulative decreases in splicing factor expression could contribute to the differential splicing, circular RNA accumulation, and defective visual behavior observed in aging photoreceptors.
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spelling pubmed-61565392018-10-01 Proper splicing contributes to visual function in the aging Drosophila eye Stegeman, Rachel Hall, Hana Escobedo, Spencer E. Chang, Henry C. Weake, Vikki M. Aging Cell Original Articles Changes in splicing patterns are a characteristic of the aging transcriptome; however, it is unclear whether these age‐related changes in splicing facilitate the progressive functional decline that defines aging. In Drosophila, visual behavior declines with age and correlates with altered gene expression in photoreceptors, including downregulation of genes encoding splicing factors. Here, we characterized the significance of these age‐regulated splicing‐associated genes in both splicing and visual function. To do this, we identified differential splicing events in either the entire eye or photoreceptors of young and old flies. Intriguingly, aging photoreceptors show differential splicing of a large number of visual function genes. In addition, as shown previously for aging photoreceptors, aging eyes showed increased accumulation of circular RNAs, which result from noncanonical splicing events. To test whether proper splicing was necessary for visual behavior, we knocked down age‐regulated splicing factors in photoreceptors in young flies and examined phototaxis. Notably, many of the age‐regulated splicing factors tested were necessary for proper visual behavior. In addition, knockdown of individual splicing factors resulted in changes in both alternative splicing at age‐spliced genes and increased accumulation of circular RNAs. Together, these data suggest that cumulative decreases in splicing factor expression could contribute to the differential splicing, circular RNA accumulation, and defective visual behavior observed in aging photoreceptors. John Wiley and Sons Inc. 2018-07-12 2018-10 /pmc/articles/PMC6156539/ /pubmed/30003673 http://dx.doi.org/10.1111/acel.12817 Text en © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Stegeman, Rachel
Hall, Hana
Escobedo, Spencer E.
Chang, Henry C.
Weake, Vikki M.
Proper splicing contributes to visual function in the aging Drosophila eye
title Proper splicing contributes to visual function in the aging Drosophila eye
title_full Proper splicing contributes to visual function in the aging Drosophila eye
title_fullStr Proper splicing contributes to visual function in the aging Drosophila eye
title_full_unstemmed Proper splicing contributes to visual function in the aging Drosophila eye
title_short Proper splicing contributes to visual function in the aging Drosophila eye
title_sort proper splicing contributes to visual function in the aging drosophila eye
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156539/
https://www.ncbi.nlm.nih.gov/pubmed/30003673
http://dx.doi.org/10.1111/acel.12817
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