2019
DOI: 10.1038/s41467-019-10508-2
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Translatome analysis reveals altered serine and glycine metabolism in T-cell acute lymphoblastic leukemia cells

Abstract: Somatic ribosomal protein mutations have recently been described in cancer, yet their impact on cellular transcription and translation remains poorly understood. Here, we integrate mRNA sequencing, ribosome footprinting, polysomal RNA sequencing and mass spectrometry datasets from a mouse lymphoid cell model to characterize the T-cell acute lymphoblastic leukemia (T-ALL) associated ribosomal RPL10 R98S mutation. Surprisingly, RPL10 R98S induces changes in protein levels primarily through… Show more

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Cited by 49 publications
(50 citation statements)
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“…In particular, combined transcriptome and translatome analysis revealed that one of the key enzymes in serine synthesis—phosphoserine phosphatase (PSPH)—is more efficiently transcribed and translated in RPL10-R98S (uL16-R98S) mutant cells. The resulting elevated serine is converted to glycine, a reaction in which one carbon is released and converted into formate, which in turn sustains nucleotide synthesis [85]. Similarly, fibroblasts of DBA patients present elevated levels of serine/glycine synthesis enzymes phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and the mitochondrial serine hydroxymethyltransferase 2 (SHMT2) [86].…”
Section: Oncogenic Mechanisms In Ribosomopathiesmentioning
confidence: 99%
“…In particular, combined transcriptome and translatome analysis revealed that one of the key enzymes in serine synthesis—phosphoserine phosphatase (PSPH)—is more efficiently transcribed and translated in RPL10-R98S (uL16-R98S) mutant cells. The resulting elevated serine is converted to glycine, a reaction in which one carbon is released and converted into formate, which in turn sustains nucleotide synthesis [85]. Similarly, fibroblasts of DBA patients present elevated levels of serine/glycine synthesis enzymes phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase 1 (PSAT1), and the mitochondrial serine hydroxymethyltransferase 2 (SHMT2) [86].…”
Section: Oncogenic Mechanisms In Ribosomopathiesmentioning
confidence: 99%
“…Consequently, FIR families, PUF60, FIR, and FIRΔexon2, potentially link among epigenetic modification, transcription, post-transcription, and alternative splicing in gene regulation. Recently, the ribosomal RPL10 R98S mutation was associated with T-cell type acute lymphocytic leukemia (T-ALL) pathogenesis [24][25][26] . Notably, FIR +/− TP53 −/− generated T-ALL 27 , indicating that FIRΔexon2 modifies ribosomal protein synthesis in cancers.…”
Section: Ribosomal Proteins and Splicing Factors Were Coimmunoprecipimentioning
confidence: 99%
“…Glycine plays a key role in regulating the methylation status of cancer cells and for DNA and RNA synthesis [36]. Recently, it has been reported that a high level of blood serine/glycine might form a protective niche for the maintenance of leukemia cells in xenografted mice [37], and that a downregulation of the glycine decarboxylase, an enzyme involved in glycine catabolism, enhances HCC progression and intrahepatic metastasis [38]. Based on this knowledge, the increased serum glycine level observed in ADV vs EAR HCC patients could be seen as a result of a reduced glycine catabolism in the advanced HCC stage.…”
Section: Discussionmentioning
confidence: 99%