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| 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
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| 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.
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| Overall design |
Ribosome_Profiling
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| 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 |
| E-mail(s) |
pedro.batista@nih.gov
|
| Phone |
3014356294
|
| Organization name |
National Institutes of Health
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| Department |
National Cancer Institute
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| Lab |
Cell Biology
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| Street address |
37 Convent Street Bldg 37
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE228565 |
Rewiring of RNA methylation by the oncometabolite fumarate in renal cell carcinoma |
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| Relations |
| BioProject |
PRJNA950373 |
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