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The Musashi proteins MSI1 and MSI2 are required for photoreceptor morphogenesis and vision in mice
The Musashi family of RNA-binding proteins is known for its role in stem-cell renewal and is a negative regulator of cell differentiation. Interestingly, in the retina, the Musashi proteins MSI1 and MSI2 are differentially expressed throughout the cycle of retinal development, with MSI2 protein disp...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948980/ https://www.ncbi.nlm.nih.gov/pubmed/33168629 http://dx.doi.org/10.1074/jbc.RA120.015714 |
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author | Sundar, Jesse Matalkah, Fatimah Jeong, Bohye Stoilov, Peter Ramamurthy, Visvanathan |
author_facet | Sundar, Jesse Matalkah, Fatimah Jeong, Bohye Stoilov, Peter Ramamurthy, Visvanathan |
author_sort | Sundar, Jesse |
collection | PubMed |
description | The Musashi family of RNA-binding proteins is known for its role in stem-cell renewal and is a negative regulator of cell differentiation. Interestingly, in the retina, the Musashi proteins MSI1 and MSI2 are differentially expressed throughout the cycle of retinal development, with MSI2 protein displaying robust expression in the adult retinal tissue. In this study, we investigated the importance of Musashi proteins in the development and function of photoreceptor neurons in the retina. We generated a pan-retinal and rod photoreceptor neuron-specific conditional KO mouse lacking MSI1 and MSI2. Independent of the sex, photoreceptor neurons with simultaneous deletion of Msi1 and Msi2 were unable to respond to light and displayed severely disrupted photoreceptor outer segment morphology and ciliary defects. Mice lacking MSI1 and MSI2 in the retina exhibited neuronal degeneration, with complete loss of photoreceptors within 6 months. In concordance with our earlier studies that proposed a role for Musashi proteins in regulating alternative splicing, the loss of MSI1 and MSI2 prevented the use of photoreceptor-specific exons in transcripts critical for outer segment morphogenesis, ciliogenesis, and synaptic transmission. Overall, we demonstrate a critical role for Musashi proteins in the morphogenesis of terminally differentiated photoreceptor neurons. This role is in stark contrast with the canonical function of these two proteins in the maintenance and renewal of stem cells. |
format | Online Article Text |
id | pubmed-7948980 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-79489802021-03-19 The Musashi proteins MSI1 and MSI2 are required for photoreceptor morphogenesis and vision in mice Sundar, Jesse Matalkah, Fatimah Jeong, Bohye Stoilov, Peter Ramamurthy, Visvanathan J Biol Chem Research Article The Musashi family of RNA-binding proteins is known for its role in stem-cell renewal and is a negative regulator of cell differentiation. Interestingly, in the retina, the Musashi proteins MSI1 and MSI2 are differentially expressed throughout the cycle of retinal development, with MSI2 protein displaying robust expression in the adult retinal tissue. In this study, we investigated the importance of Musashi proteins in the development and function of photoreceptor neurons in the retina. We generated a pan-retinal and rod photoreceptor neuron-specific conditional KO mouse lacking MSI1 and MSI2. Independent of the sex, photoreceptor neurons with simultaneous deletion of Msi1 and Msi2 were unable to respond to light and displayed severely disrupted photoreceptor outer segment morphology and ciliary defects. Mice lacking MSI1 and MSI2 in the retina exhibited neuronal degeneration, with complete loss of photoreceptors within 6 months. In concordance with our earlier studies that proposed a role for Musashi proteins in regulating alternative splicing, the loss of MSI1 and MSI2 prevented the use of photoreceptor-specific exons in transcripts critical for outer segment morphogenesis, ciliogenesis, and synaptic transmission. Overall, we demonstrate a critical role for Musashi proteins in the morphogenesis of terminally differentiated photoreceptor neurons. This role is in stark contrast with the canonical function of these two proteins in the maintenance and renewal of stem cells. American Society for Biochemistry and Molecular Biology 2020-11-22 /pmc/articles/PMC7948980/ /pubmed/33168629 http://dx.doi.org/10.1074/jbc.RA120.015714 Text en © 2020 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Sundar, Jesse Matalkah, Fatimah Jeong, Bohye Stoilov, Peter Ramamurthy, Visvanathan The Musashi proteins MSI1 and MSI2 are required for photoreceptor morphogenesis and vision in mice |
title | The Musashi proteins MSI1 and MSI2 are required for photoreceptor morphogenesis and vision in mice |
title_full | The Musashi proteins MSI1 and MSI2 are required for photoreceptor morphogenesis and vision in mice |
title_fullStr | The Musashi proteins MSI1 and MSI2 are required for photoreceptor morphogenesis and vision in mice |
title_full_unstemmed | The Musashi proteins MSI1 and MSI2 are required for photoreceptor morphogenesis and vision in mice |
title_short | The Musashi proteins MSI1 and MSI2 are required for photoreceptor morphogenesis and vision in mice |
title_sort | musashi proteins msi1 and msi2 are required for photoreceptor morphogenesis and vision in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948980/ https://www.ncbi.nlm.nih.gov/pubmed/33168629 http://dx.doi.org/10.1074/jbc.RA120.015714 |
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