PUBLICATION

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

Authors

Henson, H.E., Taylor, M.R.

ID

ZDB-PUB-201028-1

Date

2020

Source

Cells 9(11): (Journal)

Registered Authors

Taylor, Michael R.

Keywords

RNA-Seq, central nervous system, sart1, zebrafish

MeSH Terms

Ribonucleoproteins, Small Nuclear/genetics*
Phenotype
Apoptosis/genetics
Cloning, Molecular
Neurodevelopmental Disorders/diagnosis*
Neurodevelopmental Disorders/etiology*
Genetic Predisposition to Disease*
Genetic Association Studies
Caspase 3/metabolism
Exome Sequencing
Spliceosomes/metabolism
Mutation*
Animals
Computational Biology/methods
Central Nervous System/abnormalities*
Central Nervous System/metabolism*
Sequence Analysis, RNA
Disease Models, Animal

(all 18)

PubMed

33105605 Full text @ Cells

Abstract

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.

Genes / Markers

Figures

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Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
sart1^zf633/zf633 (TL)	standard conditions	Protruding-mouth	brain sart1 expression increased amount, abnormal	Fig. 4
sart1^zf633/zf633 (TL)	standard conditions	Protruding-mouth	brain ab-sv2 labeling increased amount, abnormal	Fig. 5
sart1^zf633/zf633 (TL)	standard conditions	Protruding-mouth	brain apoptotic process increased process quality, abnormal	Fig. 5
sart1^zf633/zf633 (TL)	standard conditions	Protruding-mouth	brain astrocyte decreased amount, abnormal	Fig. 5
sart1^zf633/zf633 (TL)	standard conditions	Protruding-mouth	brain neuron decreased amount, abnormal	Fig. 5
sart1^zf633/zf633 (TL)	standard conditions	Protruding-mouth	brain vasculature decreased amount, abnormal	Fig. 5
sart1^zf633/zf633 (TL)	standard conditions	Protruding-mouth	ciliary marginal zone dlc expression decreased amount, abnormal	Fig. S1
sart1^zf633/zf633 (TL)	standard conditions	Protruding-mouth	ciliary marginal zone dlc expression spatial pattern, abnormal	Fig. S1
sart1^zf633/zf633 (TL)	standard conditions	Protruding-mouth	eye ab-sv2 labeling absent, abnormal	Fig. 5
sart1^zf633/zf633 (TL)	standard conditions	Protruding-mouth	eye apoptotic process increased process quality, abnormal	Fig. 5

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
sj2Tg	Et(TETRE:EGFP)	Transgenic Insertion
zf633		Point Mutation	sart1

Human Disease / Model

Sequence Targeting Reagents

Fish

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Henson et al., 2020 ZDB-PUB-201028-1 PMID:33105605

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

Henson et al., 2020

ZDB-PUB-201028-1
PMID:33105605