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Series GSE287253 Query DataSets for GSE287253
Status Public on Jan 21, 2025
Title Catalytic activity of nuclear METTL3 promotes functional m6A modifications that drive retinal development [RNA-Seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary METTL3 catalyzes N6-methyladenosine (m6A) on mRNA, regulating RNA metabolism, but its role in early retinal development remains virtually unstudied. Using stem cell-derived 3D retinal organoids to model retinal progenitor cell (RPC) differentiation, we found that loss of METTL3 nuclear m6A enzymatic activity impairs formation of the Rx+ retinal anlage in vitro. Through dCas13b-FTO m6A engineering, we demonstrate that m6A modifications at the Six3 3'UTR control its stability. While Mettl3 loss altered histone modifications, direct METTL3 chromatin targets were not transcriptionally functional. Integration of transcriptome-wide m6A and protein-RNA mapping with a degron-based strategy revealed immediate effects of METTL3 degradation in RPCs, uncovering a regulatory interaction between METTL3 and its RNA target Ythdf1. We demonstrate uncoupling of chromatin accessibility from changes in retinal transcription and m6A modifications. In vivo studies of Mettl3-deficient RPCs showed altered cell cycle and impaired retinal ganglion cell generation. Our findings establish METTL3-dependent m6A modifications as an essential post-transcriptional layer that drives retinal development.
 
Overall design mRNA-seq profiling of time point assay (0hr, 1hr, 8hr and 24hr dTAG-13 treatment) at day 6 retinal organoids of Rx:GFP harboring FKBP12F36V-HA knocked into the C-terminal end of the two endogenous Mettl3 alleles .
 
Contributor(s) Xu J, Han Z, Rao R
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Jan 16, 2025
Last update date Jan 21, 2025
Contact name Zhaowei Han
E-mail(s) rickyhan@umich.edu
Organization name University of Michigan
Department Gilbert S. Omenn Department of Computational Medicine & Bioinformatics
Lab Rajesh C. Rao
Street address 1000 Wall St
City Ann Arbor
State/province Michigan
ZIP/Postal code 48105
Country USA
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (8)
GSM8742317 dTAGMTL3-0hr-1
GSM8742318 dTAGMTL3-0hr-2
GSM8742319 dTAGMTL3-1hr-1
Relations
BioProject PRJNA1211691

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

Supplementary file Size Download File type/resource
GSE287253_0hr-1hr.genes.count_tracking.txt.gz 653.0 Kb (ftp)(http) TXT
GSE287253_0hr-1hr.genes.fpkm_tracking.txt.gz 1.5 Mb (ftp)(http) TXT
GSE287253_0hr-24hr.genes.count_tracking.txt.gz 649.9 Kb (ftp)(http) TXT
GSE287253_0hr-24hr.genes.fpkm_tracking.txt.gz 1.5 Mb (ftp)(http) TXT
GSE287253_0hr-8hr.genes.count_tracking.txt.gz 646.8 Kb (ftp)(http) TXT
GSE287253_0hr-8hr.genes.fpkm_tracking.txt.gz 1.5 Mb (ftp)(http) TXT
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