Fitzsimmons et al. 2024 (PRJNA950373)

General Details

Title Rewiring of RNA methylation by the oncometabolite fumarate in renal cell carcinoma [Ribosome_Profiling]
Organism
Number of Samples 18
Release Date 2023/03/30 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP430136
ENA SRP430136
GEO GSE228561
BioProject PRJNA950373

Publication

Title
Authors Fitzsimmons CM,Mandler MD,Lunger JC,Chan D,Maligireddy SS,Schmiechen AC,Gamage ST,Link C,Jenkins LM,Chan K,Andresson T,Crooks DR,Meier JL,Linehan WM,Batista PJ
Journal NAR cancer
Publication Date 2024 Mar
Abstract Metabolic reprogramming is a hallmark of cancer that facilitates changes in many adaptive biological processes. Mutations in the tricarboxylic acid 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 an aggressive form of kidney cancer. Fumarate has been shown to inhibit 2-oxoglutarate-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 affects the levels of N6-methyladenosine (m 6 A), while the levels of 5-formylcytosine (f 5 C) in mitochondrial tRNA are unaffected. This supports the hypothesis of a differential impact of fumarate accumulation on distinct RNA demethylases. The observation that metabolites modulate specific subsets of RNA-modifying enzymes offers new insights into the intersection between metabolism and the epitranscriptome. Published by Oxford University Press on behalf of NAR Cancer 2024.
PMC PMC10849186
PMID 38328795
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR24017328 PRJNA950373 Homo sapiens UOK262renal cell carcinoma RNA-Seq
SRR24017325 PRJNA950373 Homo sapiens UOK262renal cell carcinoma RNA-Seq
SRR24017326 PRJNA950373 Homo sapiens UOK262renal cell carcinoma RNA-Seq
SRR24017322 PRJNA950373 Homo sapiens UOK262renal cell carcinoma Ribo-Seq
SRR24017319 PRJNA950373 Homo sapiens UOK262renal cell carcinoma Ribo-Seq
SRR24017320 PRJNA950373 Homo sapiens UOK262renal cell carcinoma Ribo-Seq
SRR24017316 PRJNA950373 Homo sapiens UOK262renal cell carcinoma RNA-Seq
SRR24017313 PRJNA950373 Homo sapiens UOK262renal cell carcinoma RNA-Seq
SRR24017314 PRJNA950373 Homo sapiens UOK262renal cell carcinoma RNA-Seq
SRR24017310 PRJNA950373 Homo sapiens UOK262renal cell carcinoma Ribo-Seq
SRR24017307 PRJNA950373 Homo sapiens UOK262renal cell carcinoma Ribo-Seq
SRR24017308 PRJNA950373 Homo sapiens UOK262renal cell carcinoma Ribo-Seq
SRR24017323 PRJNA950373 Homo sapiens UOK262renal cell carcinoma Ribo-Seq
SRR24017324 PRJNA950373 Homo sapiens UOK262renal cell carcinoma Ribo-Seq
SRR24017321 PRJNA950373 Homo sapiens UOK262renal cell carcinoma Ribo-Seq
SRR24017311 PRJNA950373 Homo sapiens UOK262renal cell carcinoma Ribo-Seq
SRR24017312 PRJNA950373 Homo sapiens UOK262renal cell carcinoma Ribo-Seq
SRR24017309 PRJNA950373 Homo sapiens UOK262renal cell carcinoma 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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