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Pseudouridylation of tRNA-derived fragments steers translation control in stem cells

ABSTRACT: Pseudouridylation of tRNA-derived fragments steers translation control in stem cells

OTHER RELATED OMICS DATASETS IN: PXD008676GSE101006

PROVIDER: PRJNA393586 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11833200.fastq.gz	Fastqsanger.gz
	SRR11833201.fastq.gz	Fastqsanger.gz
	SRR11833202.fastq.gz	Fastqsanger.gz
	SRR11833203.fastq.gz	Fastqsanger.gz
	SRR11833204.fastq.gz	Fastqsanger.gz

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Pseudouridylation of tRNA-derived fragments steers translation control in stem cells [iCLIP]

Project description:Pseudouridylation (Ψ) is the most abundant and widespread type of RNA epigenetic modification in living organisms; however, the biological role of Ψ remains poorly understood. Here, we show that a Ψ-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenesis. Mechanistically, the Ψ ‘writer’ PUS7 modifies and activates a network of tRNA-derived fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translational regulation leading to high protein biosynthesis and abnormal germ layer specification. Dysregulation of PUS7 and tRFs in myeloid malignancies associates with altered translation rates, suggesting a role of Ψ in tumorigenesis. Our findings unveil a critical function of Ψ in directing translational control in stem cells with promisingly broad implications for human disease.

2018-04-22 | GSE101005 | GEO

Pseudouridylation of tRNA-derived fragments steers translation control in stem cells [Polysome-Seq]

Project description:Pseudouridylation (pseudouridine) is the most abundant and widespread type of RNA epigenetic modification in living organisms; however, the biological role of pseudouridine remains poorly understood. Here, we show that a pseudouridine-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenesis. Mechanistically, the pseudouridine ‘writer’ PUS7 modifies and activates a network of tRNA-derived fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translational regulation leading to high protein biosynthesis and abnormal germ layer specification. Dysregulation of PUS7 and tRFs in myeloid malignancies associates with altered translation rates, suggesting a role of pseudouridine in tumorigenesis. Our findings unveil a critical function of pseudouridine in directing translational control in stem cells with promisingly broad implications for human disease.

2018-04-09 | GSE101485 | GEO

Pseudouridylation of tRNA-derived fragments steers translation control in stem cells [small RNA-seq]

2018-04-22 | GSE101004 | GEO

Pseudouridylation of tRNA-derived fragments steers translational control in stem cells

Project description:Pseudouridylation (Ψ) is the most abundant and widespread type of RNA epigenetic modification in living organisms; however, the biological role of Ψ remains poorly understood. Here, we show that a Ψ-driven posttranscriptional program steers translation control to impact stem cell commitment during early embryogenesis. Mechanistically, the Ψ ‘writer’ PUS7 modifies and activates a network of tRNA-derived fragments (tRFs) targeting the translation initiation complex. PUS7 inactivation in embryonic stem cells impairs tRF-mediated translational regulation leading to increased protein biosynthesis and abnormal germ layer specification. Remarkably, dysregulation of PUS7 and tRFs in myeloid malignancies associates with altered translation rates, suggesting a role of Ψ in leukemogenesis. Our findings unveil a critical function of Ψ in directing translational control in stem cells with important implications for human disease.

2018-04-11 | PXD008676 | Pride

Human PUS7 in tRNA pseudouridylation

Project description:Human PUS7 in tRNA pseudouridylation

| PRJNA613911 | ENA

Pseudouridylation of tRNA-derived fragments steers translation control in stem cells

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

2018-04-22 | GSE101006 | GEO

Homo sapiens

Project description:Pseudouridylation of tRNA-derived fragments steers translation control in stem cells [iCLIP]

| PRJNA393590 | ENA

Guanosine-7 tRNA methylation steers tRNA-derived fragment biogenesis and translational control in prostate cancer

Project description:Abstract Transfer RNAs (tRNAs) are exceptionally subject to modifications, including methylation. While mRNA methylation is emerging as an important regulator of biological and pathological processes in cancer, how post-transcriptional methylation of tRNAs contributes to cancer is largely unknown. Here we show that the RNA N7-methylguanosine (m7G) methyltransferase METTL1 is highly differentially expressed in prostate cancer compared to non-tumour prostate tissues. METTL1 expression regulation is mediated by the oncogenic regulator PI3K, which is altered in most advanced prostate tumours. Knockdown of METTL1 dramatically inhibits prostate cancer cell growth and tumour progression in vivo. In contrast, overexpression of the wild type but not the catalytically inactive METTL1 potentiates cell growth. Thus, METTL1-mediated methylation is important for prostate tumorigenesis. Mechanistically we find that METTL1 depletion causes loss of m7G tRNA methylation and increases endonucleolytic cleavage of Cysteine tRNA leading to an accumulation of 5′ tRNA-derived small RNA fragments. 5′ tRNA-derived fragments steer translation control to favour synthesis of key regulators of tumour growth suppression and immune rejection. In summary, our findings uncover a critical function of m7G tRNA methylation in directing translation control in cancer cells with important implications for tumour growth and unveil METTL1 inhibition as a promising anti-cancer therapeutic strategy. induction and maintenance of naïve human pluripotency are governed by distinct signaling requirements. tRNAs from WT and METTL1 KO cells were subjected to NaBH4-Aniline treatment followed by RNA-seq to unveil methylation of guanosine-7 in tRNA with nucleotie resolution. RNA-seq libraries were also analysed to unveil tRNA stability or processing into tRNA-derived fragments in METTL1 KO cells.

2023-08-08 | GSE190911 | GEO

Homo sapiens

Project description:Pseudouridylation of tRNA-derived fragments steers translation control in stem cells [Polysome-Seq]

| PRJNA394611 | ENA

Homo sapiens

Project description:Pseudouridylation of tRNA-derived fragments steers translation control in stem cells [small RNA-seq]

| PRJNA393589 | ENA