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A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System

The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a...

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Autores principales: Henson, Hannah E., Taylor, Michael R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690441/
https://www.ncbi.nlm.nih.gov/pubmed/33105605
http://dx.doi.org/10.3390/cells9112340
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author Henson, Hannah E.
Taylor, Michael R.
author_facet Henson, Hannah E.
Taylor, Michael R.
author_sort Henson, Hannah E.
collection PubMed
description The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1’s involvement in cell death and vision-related pathways.
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spelling pubmed-76904412020-11-27 A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System Henson, Hannah E. Taylor, Michael R. Cells Article The spliceosome consists of accessory proteins and small nuclear ribonucleoproteins (snRNPs) that remove introns from RNA. As splicing defects are associated with degenerative conditions, a better understanding of spliceosome formation and function is essential. We provide insight into the role of a spliceosome protein U4/U6.U5 tri-snRNP-associated protein 1, or Squamous cell carcinoma antigen recognized by T-cells (Sart1). Sart1 recruits the U4.U6/U5 tri-snRNP complex to nuclear RNA. The complex then associates with U1 and U2 snRNPs to form the spliceosome. A forward genetic screen identifying defects in choroid plexus development and whole-exome sequencing (WES) identified a point mutation in exon 12 of sart1 in Danio rerio (zebrafish). This mutation caused an up-regulation of sart1. Using RNA-Seq analysis, we identified additional upregulated genes, including those involved in apoptosis. We also observed increased activated caspase 3 in the brain and eye and down-regulation of vision-related genes. Although splicing occurs in numerous cells types, sart1 expression in zebrafish was restricted to the brain. By identifying sart1 expression in the brain and cell death within the central nervous system (CNS), we provide additional insights into the role of sart1 in specific tissues. We also characterized sart1’s involvement in cell death and vision-related pathways. MDPI 2020-10-22 /pmc/articles/PMC7690441/ /pubmed/33105605 http://dx.doi.org/10.3390/cells9112340 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Henson, Hannah E.
Taylor, Michael R.
A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System
title A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System
title_full A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System
title_fullStr A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System
title_full_unstemmed A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System
title_short A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System
title_sort sart1 zebrafish mutant results in developmental defects in the central nervous system
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690441/
https://www.ncbi.nlm.nih.gov/pubmed/33105605
http://dx.doi.org/10.3390/cells9112340
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