Nakaya et al. 2017 (PRJNA416661)

General Details

Title	Amyotrophic Lateral Sclerosis associated FUS mutation shortens mitochondria and induces neurotoxicity
Organism
Number of Samples	3
Release Date	2017/10/31 00:00
Sequencing Types
Protocol Details

Study Links

GWIPS-viz	Trips-Viz

Repository Details

SRA	SRP123232
ENA	SRP123232
GEO
BioProject	PRJNA416661

Publication

Title
Authors	Nakaya T,Maragkakis M
Journal	Scientific reports
Publication Date	2018 Oct 22
Abstract	Amyotrophic Lateral Sclerosis (ALS) is a lethal neurodegenerative disorder that primarily affects motor neurons. Dominant mutations in the RNA binding protein Fused in Sarcoma (FUS) have been identified as causative factors of ALS. Mutation, R495X, results in a premature stop codon and induces an aggressive disease phenotype by a largely unknown process. Here, we employ CLIP-Seq, RNA-Seq and Ribo-Seq in cultured neurons expressing R495X or wild-type FUS to identify the mutation effects on the FUS targetome and on the neuronal transcriptome at the expression and translation level, simultaneously. We report that, unlike wild-type FUS that binds on precursor mRNAs (pre-mRNAs), R495X binds mature mRNAs in the cytoplasm. R495X has a moderate effect on target mRNA expression and its binding induces only modest expression changes. In contrast, we find that R495X controls the translation of genes that are associated with mitochondria function and results in significant reduction of mitochondrial size. Importantly, we show that introduction of the 4FL mutation that alters binding of R495X to RNA, partially abrogates R495X-induced effects on mRNA translation, mitochondrial size and neurotoxicity. Our findings uncover a novel RNA-mediated pathway of FUS R495X-induced neurotoxicity that affects mitochondria morphology and provide insight to previous studies associating mitochondria dysfunction to ALS.
PMC	PMC6197261
PMID	30349096
DOI

	Run Accession	Study Accession	Scientific Name	Cell Line	Library Type	Treatment	GWIPS-viz	Trips-Viz	Reads	BAM	BigWig (F)	BigWig (R)
	SRR6240171	PRJNA416661	Mus musculus	ES cell derived neurons	Ribo-Seq
	SRR6240172	PRJNA416661	Mus musculus	ES cell derived neurons	Ribo-Seq
	SRR6240173	PRJNA416661	Mus musculus	ES cell derived neurons	Ribo-Seq
	Run Accession	Study Accession	Scientific Name	Cell Line	Library Type	Treatment	GWIPS-viz	Trips-Viz	Reads	BAM	BigWig (F)	BigWig (R)

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