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TRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling [scRNA-seq]

ABSTRACT: tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling [scRNA-seq]

PROVIDER: PRJNA962329 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24321494_1.fastq.gz	Fastqsanger.gz
	SRR24321494_2.fastq.gz	Fastqsanger.gz
	SRR24321495_1.fastq.gz	Fastqsanger.gz
	SRR24321495_2.fastq.gz	Fastqsanger.gz
	SRR24321496_1.fastq.gz	Fastqsanger.gz

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tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling

Project description:tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling

| PRJNA1063223 | ENA

tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling [mim-tRNAseq]

Project description:tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling [mim-tRNAseq]

| PRJNA1063221 | ENA

tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling [scRNA-seq]

Project description:Hematopoietic stem cells (HSCs) have some unique physiological adaptations to maintain blood cell production and deal with stress responses throughout life. To maintain such adaptations, HSCs are particularly dependent on maintaining a tightly controlled protein translation rate. However, how HSCs fine tune protein translation has not been fully described. In this study, we report the role of TRMT6 in regulating HSC function in adult hematopoiesis. Trmt6-null mice became moribund due to hematopoietic failure with pancytopenia in the blood and bone marrow 4 to 8 weeks after Trmt6 deletion. Trmt6-deleted bone marrow cells failed to repopulate hemoablated recipients in competitive transplantation experiments. Loss of TRMT6 resulted in an abnormally high rate of recruitment of quiescent hematopoietic stem cells (HSCs) into the cell cycle. Cycling HSCs produced progenitors at the expense of self-renewal, which led to the exhaustion of the HSC pool. Mechanistically, mTORC1 signaling pathway was highly upregulated in HSC-enriched cell populations after Trmt6 deletion by single cell RNA-seq analysis. Furthermore, TRMT6 was required for tRNA m1A modification required for HSC quiescence and self-renewal. Our data indicate that TRMT6 promotes the expression of TSC1, fine-tuning mTORC1 signaling level which is essential for HSC maintenance and self-renewal in adult hematopoiesis.

2024-06-03 | GSE230711 | GEO

Prokaryotic N1-methyladenosine erasers maintain tRNA m1A modification levels in Streptomyces venezuelae.

Project description:tRNA modifications help maintain tRNA structure and facilitate stress responses. Found in all three kingdoms of life, m1A tRNA modification occurs in the T loop of many tRNAs and stabilizes tertiary tRNA structure and impacts translation. M1A in T loop is known to be reversible by three mammalian demethylase enzymes, which bypasses the need of turning over the tRNA molecule to adjust their m1A levels in cells. However, no prokaryotic tRNA demethylase enzyme has been identified. Using Streptomyces venezuelae as a model organism, we confirmed the presence and quantitative m1A tRNA signatures using mass spectrometry and high throughput tRNA sequencing. We identified two RNA demethylases that can remove m1A in tRNA and confirmed the activity of a previously annotated tRNA m1A writer. Using single gene knockouts of these erasers and the m1A writer, we subjected these strains to stress conditions and found dynamic changes to m1A levels in many tRNAs. Phenotypic characterization highlighted changes to their growth and altered antibiotic production. Our identification of the first prokaryotic tRNA demethylase enzyme paves the way for investigating new mechanisms in global translational regulation in bacteria.

2024-06-20 | GSE264330 | GEO

tRNA m1A modification regulate hematopoietic stem cell maintenance via mTORC1 signaling [mim-tRNAseq]

Project description:High-resolution quantitative profiling of tRNA abundance and modification status in hematopoietic cells upon Trmt6 deletion by mim-tRNAseq

2024-06-03 | GSE252912 | GEO

TRMT6-mediated tRNA m1A modification serves as a translational checkpoint of histone biosynthesis and facilitates colorectal cancer progression [tRNA]

Project description:Reprogramming of mRNA translation drives malignant transformation and cancer development. Recently, increasing studies have demonstrated that tRNA modification emerges as a critical regulator of translational reprogramming; however, its function in cancers remains largely elusive. Herein, we identify the oncogenic role of tRNA N1-methyladenosine (m1A) modification in colorectal cancer (CRC). Targeting m1A methyltransferase TRMT6 in CRC cells decreases the abundance of a specific subset of tRNAs (e.g., tRNA-Arg-ACG-1-1, tRNA-Lys-TTT-1-1) and impairs histone mRNA translation in a codon-biased manner, thus restricting histone biosynthesis and cell cycle progression. We further demonstrate that the combination of TRMT6 inhibition and CDK4/6 inhibition shows a stronger anti-cancer effect on CRC cells by synergistically inhibit histone biosynthesis. Collectively, our study reveals that tRNA m1A modification acts as a translational checkpoint of histone biosynthesis and promotes CRC progression, providing new insights for the development of efficient therapeutic strategies against CRC.

2025-02-08 | GSE233354 | GEO

tRNA m1A modification regulates cholesterol biosynthesis to promote antitumor immunity of CD8+ T cells

Project description:Activation of CD8+ T cells necessitates rapid metabolic reprogramming to fulfill the substantial biosynthetic demands of their effector functions. However, the post-transcriptional mechanisms underpinning this process remain obscure. The tRNA N1-methyladenine (m1A) modification, which plays a role in maintaining tRNA stability and modulating protein translation, has an undefined physiological function in CD8+ T cells, particularly in antitumor responses. Here, we demonstrate that the tRNA m1A 'writer' gene Trmt61a enhances the tumor-killing capacity of CD8+ T cells by regulating cholesterol biosynthesis. We find that Trmt61a expression in CD8+ T cells is upregulated upon activation and correlates positively with T cell-mediated cytotoxicity within the tumor microenvironment of colorectal cancer (CRC) patients. Deletion of Trmt61a in CD8+ T cells leads to a compromised tumor-killing function in both in vivo and in vitro assays, which is dependent on the m1A catalytic activity of TRMT61A. Mechanistically, tRNA m1A promotes antitumor immunity in CD8+ T cells by enhancing the translation of ATP citrate lyase (ACLY), a key enzyme for cholesterol biosynthesis. Supplementation with cholesterol can rescue the impaired tumor-killing function and proliferation of TRMT61A-deficient CD8+ T cells. Our findings underscore the significance of tRNA m1A modification as a regulatory checkpoint in cholesterol metabolism in CD8+ T cells, suggesting potential novel strategies for cancer immunotherapy.

2025-01-07 | GSE275602 | GEO

Chemical manipulation of m1A mediates its detection in human tRNA

Project description:N1-methyl adenosine (m1A) is a wide-spread RNA modification present in tRNA, rRNA and mRNA. m1A modification sites in tRNAs are evolutionary conserved and its formation on tRNA is catalyzed by methyltransferase TRMT61A and TRMT6 complex. m1A promotes translation initiation and elongation. Due to its positive charge under physiological conditions, m1A can notably modulate RNA structure. It also blocks Watson-Crick base pairing and causes mutation and truncation during reverse transcription. Several misincorporation-based high throughput sequencing methods have been developed to sequence m1A. In this study, we introduce a reduction-based m1A sequencing (red-m1A-seq). We report that NaBH4 reduction of m1A can improve the mutation and readthrough rates using commercially available RT enzymes to give better positive signature, while alkaline-catalyzed Dimroth rearrangement can efficiently convert m1A to m6A to provide good controls, allowing the detection of m1A with higher sensitivity and accuracy. We applied red‑m1A-seq to sequence human small RNA and we not only detected all the previously reported tRNA m1A sites, but also new m1A sites in mt-tRNAAsn-ATT and 5.8S rRNA.

2024-04-24 | GSE253657 | GEO

TRMT6-mediated tRNA m1A modification serves as a translational checkpoint of histone biosynthesis and facilitates colorectal cancer progression [Ribo]

2025-02-08 | GSE233358 | GEO

TRMT6-mediated tRNA m1A modification serves as a translational checkpoint of histone biosynthesis and facilitates colorectal cancer progression [RNA]

2025-02-08 | GSE233356 | GEO