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Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia [RNAseq]

ABSTRACT: We report the effects on gene expression on dietary modulation of valine in an in vivo model of T cell acute lymphoblastic leukemia

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE165661 | GEO | 2021/10/27

REPOSITORIES: GEO

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Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia [Ribo-Seq]

Project description:We report the effects on gene expression at the translational level on dietary modulation of valine in in vivo model of T cell acute lymphoblastic leukemia

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Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia [CRISPR screen]

Project description:We report the effects of gene knockout via CRISPR/Cas9 system targeting either the whole genome or specifically genes involved in tRNA biogenesis in T cell acute lymphoblastic leukemia cell lines under normal versus valine limited media.

2021-10-27 | GSE167534 | GEO

Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia [tRNAseq]

Project description:We report the effects on changes in tRNA expression in T cell acute lymphoblastic leukemia relative to CD4 T cells.

2021-10-27 | GSE165734 | GEO

Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia [RNAseq]

Project description:Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia [RNAseq]

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Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-10-25 | GSE165736 | GEO

Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia

Project description:Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia

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Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia [tRNAseq]

Project description:Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia [tRNAseq]

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Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia [CRISPR screen]

Project description:Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia [CRISPR screen]

| PRJNA704906 | ENA

Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia [Ribo-Seq]

Project description:Valine tRNA biogenesis and bioavailability regulates mitochondrial complex I levels in acute leukemia [Ribo-Seq]

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Valine tRNA levels and availability regulate complex I assembly in leukaemia.

Project description:Although deregulation of transfer RNA (tRNA) biogenesis promotes the translation of pro-tumorigenic mRNAs in cancers1,2, the mechanisms and consequences of tRNA deregulation in tumorigenesis are poorly understood. Here we use a CRISPR-Cas9 screen to focus on genes that have been implicated in tRNA biogenesis, and identify a mechanism by which altered valine tRNA biogenesis enhances mitochondrial bioenergetics in T cell acute lymphoblastic leukaemia (T-ALL). Expression of valine aminoacyl tRNA synthetase is transcriptionally upregulated by NOTCH1, a key oncogene in T-ALL, underlining a role for oncogenic transcriptional programs in coordinating tRNA supply and demand. Limiting valine bioavailability through restriction of dietary valine intake disrupted this balance in mice, resulting in decreased leukaemic burden and increased survival in vivo. Mechanistically, valine restriction reduced translation rates of mRNAs that encode subunits of mitochondrial complex I, leading to defective assembly of complex I and impaired oxidative phosphorylation. Finally, a genome-wide CRISPR-Cas9 loss-of-function screen in differential valine conditions identified several genes, including SLC7A5 and BCL2, whose genetic ablation or pharmacological inhibition synergized with valine restriction to reduce T-ALL growth. Our findings identify tRNA deregulation as a critical adaptation in the pathogenesis of T-ALL and provide a molecular basis for the use of dietary approaches to target tRNA biogenesis in blood malignancies.

| S-EPMC9116157 | biostudies-literature

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