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Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming (RNA-Seq)

ABSTRACT: To understand the underlying mechanism of YRDC, an enzyme catalysing the formation of N6-threonylcarbamoyladenosine (t6A) on ANN-decoding tRNAs, and the interplay between threonine and YRDC in glioblastoma stem cells (GSCs), we carried out comparative transcriptomic analysis in patient-derived GSC456 with or without YRDC deprivation and with or without threonine restriction (control media, 800 μM threonine; threonine-restricted media, 4 μM). To further investigate the translational regulation of YRDC and threonine in GSCs, we performed ribosome profiling in GSC456 with or without YRDC deprivation and with or without threonine restriction (control media, 800 μM threonine; threonine-restricted media, 4 μM).

ORGANISM(S): Homo sapiens

PROVIDER: GSE229671 | GEO | 2024/01/06

REPOSITORIES: GEO

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Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming (tRNA-Seq)

Project description:To understand the underlying mechanism of YRDC, an enzyme catalysing the formation of N6-threonylcarbamoyladenosine (t6A) on ANN-decoding tRNAs, and the interplay between threonine and YRDC in glioblastoma stem cells (GSCs), we carried out comparative transcriptomic analysis in patient-derived GSC456 with or without YRDC deprivation and with or without threonine restriction (control media, 800 μM threonine; threonine-restricted media, 4 μM). To further investigate the translational regulation of YRDC and threonine in GSCs, we performed ribosome profiling in GSC456 with or without YRDC deprivation and with or without threonine restriction (control media, 800 μM threonine; threonine-restricted media, 4 μM). To investigate the effects of YRDC and threonine purtubation on tRNA expression in GSCs, we performed tRNA sequencing in GSC456 with or without YRDC deprivation and with or without threonine restriction (control media, 800 μM threonine; threonine-restricted media, 4 μM).

2024-01-06 | GSE245043 | GEO

Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming (Ribosome profiling)

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Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming

Project description:Cancers commonly reprogram translation and metabolism, but little is known about how these two features coordinate in cancer stem cells. Here, we show that glioblastoma stem cells (GSCs) display elevated protein translation. To dissect underlying mechanisms, we performed a CRISPR screen and identified YRDC as the top essential tRNA modification enzymes in GSCs. YRDC catalyses the formation of N6-threonylcarbamoyladenosine (t6A) on ANN-decoding tRNAs (A denotes adenosine and N denotes any nucleotide). Targeting YRDC reduced t6A formation, suppressed global translation, and inhibited tumour growth both in vitro and in vivo. Threonine is an essential substrate of YRDC. Threonine accumulated in GSCs, which facilitated t6A formation through YRDC and shifted the proteome to support mitosis-related genes with ANN codon-bias. Dietary threonine restriction (TR) reduced tumour t6A formation, slowed xenograft growth, and augmented anti-tumour efficacy of chemotherapy and anti-mitotic therapy, providing a molecular basis for a dietary intervention in cancer treatment.

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Lysine Degradation Reprograms Tumour Immunity through Histone Crotonylation [ChIP-seq]

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The effect of MPO inhibitor on the gene expression profiles in HL-60 cell lines exposed to 1, 2, 4,-benzenetriol

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