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Series GSE228561 Query DataSets for GSE228561
Status Public on Feb 15, 2024
Title Rewiring of RNA methylation by the oncometabolite fumarate in renal cell carcinoma [Ribosome_Profiling]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Metabolic reprogramming is a hallmark of cancer that facilitates changes in many adaptive biological processes. Mutations in the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase (FH) lead to fumarate accumulation and cause hereditary leiomyomatosis and renal cell cancer (HLRCC). HLRCC is a rare, inherited disease characterized by the development of non-cancerous smooth muscle tumors of the uterus and skin, and an increased risk of a highly metastatic and aggressive form of kidney cancer. Fumarate has been shown to inhibit 2-oxyglutarate-dependent dioxygenases (2OGDDs) involved in the hydroxylation of HIF1α, as well as in DNA and histone demethylation. However, the link between fumarate accumulation and changes in RNA post-transcriptional modifications has not been defined. Here, we determine the consequences of fumarate accumulation on the activity of different members of the 2OGDD family targeting RNA modifications. By evaluating multiple RNA modifications in patient-derived HLRCC cell lines, we show that mutation of FH selectively alters the activity of demethylases acting upon N6-methyladenosine (m6A), while the demethylases acting upon N1-methyladenosine (m1A) and 5-formylcytosine (f5C) in mitochondrial RNA are unaffected. The observation that metabolites may modulate specific subsets of RNA-modifying enzymes offers new insights into their gene regulatory effects and potential strategies for therapeutic intervention.
Overall design Ribosome_Profiling
Contributor(s) Fitzsimmons CM, Mandler MD, Lunger JC, Chan D, Maligireddy SS, Schmiechen AC, Gamage ST, Link C, Jenkins LM, Crooks DR, Meier JL, Linehand WM, Batista PJ
Citation(s) 38328795
Submission date Mar 30, 2023
Last update date Feb 16, 2024
Contact name Pedro J Batista
Phone 3014356294
Organization name National Institutes of Health
Department National Cancer Institute
Lab Cell Biology
Street address 37 Convent Street Bldg 37
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (12)
GSM7124082 Run 1 mutant input replicate 1
GSM7124083 Run 1 mutant input replicate 2
GSM7124084 Run 1 mutant input replicate 3
This SubSeries is part of SuperSeries:
GSE228565 Rewiring of RNA methylation by the oncometabolite fumarate in renal cell carcinoma
BioProject PRJNA950373

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
GSE228561_RAW.tar 2.6 Mb (http)(custom) TAR (of TXT)
GSE228561_Riboseq_counts_table_R.txt.gz 547.6 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record
Processed data provided as supplementary file

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