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Series GSE203579 Query DataSets for GSE203579
Status Public on Jun 09, 2023
Title N6-methyladenosine regulates RNA metabolism and neurodegeneration in C9ORF72-ALS/FTD [seq_polyA_RNA-decay]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary N6-methyladenosine (m6A) is the most prevalent internal mRNA modification and regulates RNA metabolism. Repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Here, we showed that m6A is downregulated in C9ORF72-ALS/FTD patient-derived iPSC-differentiated neurons and postmortem brain tissues. The global m6A hypomethylation leads to transcriptome-wide mRNA stabilization and upregulated gene expression, especially ones involved in synaptic activity and neuronal functions. The m6A modification in the C9ORF72 intron sequence preceding the expanded repeats enhances RNA degradation via the nuclear reader YTHDC1. The m6A reduction leads to increased accumulation of repeat RNA and poly-dipeptides. Moreover, the antisense RNA can also be regulated by m6A. Elevating m6A level significantly reduces both sense and antisense repeat RNA and poly-dipeptides, rescues global mRNA homeostasis, and improves survival of C9ORF72-ALS/FTD patient neurons.
 
Overall design The neurons at day 32 of differentiation were treated with actinomycin D to halt de novo transcription, and RNAs were collected 0, 3, and 6 hours after treatment for RNA-seq to quantify the transcriptome-wide mRNA half-life.
 
Contributor(s) Li Y, Dou X, He C, Sun S
Citation(s) 37365312
Submission date May 23, 2022
Last update date Sep 05, 2023
Contact name Chuan He
E-mail(s) chuanhe@uchicago.edu
Phone 773-702-5061
Organization name University of Chicago
Department Department of Chemistry
Street address 929 E 57th St., GCIS E319
City Chicago
State/province ILLINOIS
ZIP/Postal code 60637
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (18)
GSM6176473 iPSN-C9-1_0h
GSM6176474 iPSN-C9-1_3h
GSM6176475 iPSN-C9-1_6h
This SubSeries is part of SuperSeries:
GSE203581 Globally reduced N6-methyladenosine (m6A) in C9ORF72-ALS/FTD dysregulates RNA metabolism and contributes to neurodegeneration
Relations
BioProject PRJNA841495

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE203579_RAW.tar 4.2 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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