Drosophila melanogaster
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB16512 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| DRR499643_1.fastq.gz | Fastqsanger.gz | |||
| DRR499643_2.fastq.gz | Fastqsanger.gz | |||
| DRR499644_1.fastq.gz | Fastqsanger.gz | |||
| DRR499644_2.fastq.gz | Fastqsanger.gz | |||
| DRR499645_1.fastq.gz | Fastqsanger.gz |
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Project description:N7-methylguanosine (m7G) in variable loop region of tRNA stabilizes target tRNA expression, which is catalyzed by METTL1/WDR4 heterodimer. Here, we unveil essential functions of Mettl1 in Drosophila fertility. Mettl1-knockout (Mettl1-KO) decreases elongated spermatid and mature sperm, which is fully rescued by Mettl1-transgene expression, but not catalytic dead Mettl1-transgene, demonstrating that Mettl1-dependent m7G is required for spermatogenesis. Mettl1-KO shows loss of m7G modification on subset of tRNAs and decreased level of tRNA expression. Strikingly, overexpression of translational elongation factor EF1α that can compete with rapid tRNA decay (RTD) pathway in S. cerevisiae, significantly counteract the sterility in Mettl1-KO male, supporting a critical role of m7G tRNA modification in spermatogenesis. Ribo-seq analysis shows that Mettl1-KO elevates ribosome collisions at codons decoded by reduced tRNAs and significantly reduces translation of genes involved in elongated spermatid formation and sperm stability. These findings reveal a developmental role for m7G tRNA modifications and suggest that m7G modification-dependent tRNA stability differs among tissues.
2024-08-16 | GSE241519 | GEO
Project description:Mettl1-dependent m7G tRNA modification is essential for maintaining fertility and proper spermatogenesis in Drosophila melanogaster
| PRJNA1008576 | ENA
Project description:The tRNA N7-methylguanosine (m7G) modification is not essential for yeast growth, but in mammals mis-regulations of tRNA m7G modification cause stem cell defect and developmental disorders. Here we found that tRNA m7G methyltransferase complex components METTL1 and WDR4 are elevated in lung cancer tissues and associated with poor lung cancer prognosis. Functionally, depletion of METTL1 or WDR4 suppresses proliferation, migration, and invasion of lung cancer cells. In addition, forced expression of METTL1 or WDR4 promotes lung cancer progression depending on the tRNA m7G methyltransferase activity. Mechanistically, METTL1 knockdown leads to reduced tRNA m7G modification and decreased expression of m7G-modified tRNAs. Depletion of METTL1 selectively reduces the translation of a subset of oncogenic transcripts, including the genes related to cell proliferation in a m7G related codon dependent manner. Our study uncovered a new layer of translation regulation mechanism mediated by tRNA m7G modification, provided strong evidence to support the important physiological function of mis-regulated tRNA modification in cancer, and suggested that targeting METTL1 could be a promising strategy for lung cancer treatment.
2022-12-31 | GSE173750 | GEO
Project description:The tRNA N7-methylguanosine (m7G) modification is not essential for yeast growth, but in mammals mis-regulations of tRNA m7G modification cause stem cell defect and developmental disorders. Here we found that tRNA m7G methyltransferase complex components METTL1 and WDR4 are elevated in lung cancer tissues and associated with poor lung cancer prognosis. Functionally, depletion of METTL1 or WDR4 suppresses proliferation, migration, and invasion of lung cancer cells. In addition, forced expression of METTL1 or WDR4 promotes lung cancer progression depending on the tRNA m7G methyltransferase activity. Mechanistically, METTL1 knockdown leads to reduced tRNA m7G modification and decreased expression of m7G-modified tRNAs. Depletion of METTL1 selectively reduces the translation of a subset of oncogenic transcripts, including the genes related to cell proliferation in a m7G related codon dependent manner. Our study uncovered a new layer of translation regulation mechanism mediated by tRNA m7G modification, provided strong evidence to support the important physiological function of mis-regulated tRNA modification in cancer, and suggested that targeting METTL1 could be a promising strategy for lung cancer treatment.
2022-12-31 | GSE173760 | GEO
Project description:The cancer cells selectively promote the translation of oncogenic mRNAs to facilitate cancer progression, while the molecular mechanisms remain unclear. The tRNA N7-methylguanosine (m7G) modification is not essential for yeast growth, but in mammals mis-regulations of tRNA m7G modification cause stem cell defect and developmental disorders. Here we found that tRNA m7G methyltransferase complex components METTL1 and WDR4 are elevated in esophageal squamous cell carcinoma (ESCC) tissues and associated with poor ESCC prognosis. Functionally, depletion of METTL1 or WDR4 suppresses proliferation, migration, and invasion of ESCC cells. In addition, forced expression of METTL1 or WDR4 promotes ESCC progression depending on the tRNA m7G methyltransferase activity. Mechanistically, METTL1 knockdown leads to reduced tRNA m7G modification and decreased expression of m7G-modified tRNAs. Depletion of METTL1 selectively reduces the translation of a subset of oncogenic transcripts, including the genes related to mTOR signaling and autophagy in m7G related codon dependent manner. Rescue assays revealed the essential function of RPTOR/ULK1/autophagy axis in METTL1 driven ESCC progression. Furthermore, ESCC initiation and progression models using Mettl1 conditional knockout and knockin mice uncovered the strong physiological function of Mettl1 in promoting in vivo ESCC tumorigenesis. Our study uncovered a new layer of translation regulation mechanism mediated by tRNA m7G modification, provided strong evidence to support the important physiological function of mis-regulated tRNA modification in cancer, and suggested that targeting METTL1 and its downstream signaling axis could be a promising strategy for ESCC treatment.
2022-02-16 | GSE169590 | GEO
Project description:N7-methylguanosine (m7G) modification is one of the most prevalent tRNA modifications in human. The precise function and molecular mechanism of m7G tRNA modification in regulation of cancer remain poorly understood. Here we showed that m7G tRNA modification, METTL1 and WDR4 are elevated in hepatocellular carcinoma (HCC) tissues and associated with HCC patient prognosis. Functionally, silencing METTL1 or WDR4 inhibits HCC cell proliferation, migration and invasion, while forced expression of wild type METTL1 but not its catalytic dead mutant promotes HCC progression. Knockdown of METTL1 reduces m7G tRNA modification and decreases m7G modified tRNA expression. Mechanistically, METTL1 depletion selectively decreases the mRNA translation of a subset of oncogenic genes, especially cell cycle and EGFR pathway genes, in m7G-related codon dependent manner. Moreover, in vivo studies using Mettl1 knock-in and knockout mice reveal a critical function of Mettl1 mediated m7G tRNA modifications in promoting hepatocarcinogenesis in the hydrodynamics transfection HCC model. Our work uncovers the critical functions of tRNA m7G modification in regulating cancer mRNA translation and promoting hepatocarcinogenesis, thus provides new insights into role of the mis-regulated tRNA modifications in cancers.
2021-06-26 | GSE174492 | GEO
Project description:Treatment selections are very limited for patients with advanced nasopharyngeal carcinoma (NPC) experiencing disease progression. Uncovering the potential mechanism underlying NPC progression is crucial for identify novel treatments. Here we show that N7-methylguanosine (m7G) tRNA modification enzyme METTL1 and its partner WDR4 are significantly elevated in NPC and associated with poor prognosis. Loss-of-function and gain-of-function assays demonstrated that METTL1/WDR4 mediated m7G tRNA modification promotes NPC growth and metastasis in vitro and in vivo. Mechanistically, m7G tRNA modification selectively regulates the translation of transcripts with higher percentage of m7G tRNA decoded codons. Moreover, further analysis revealed that METTL1-mediated m7G tRNA modification activates WNT/β-Catenin signaling pathway to promote NPC cell epithelial-mesenchymal transition (EMT) and chemoresistance to cisplatin and docetaxel in vitro and in vivo. Our work uncovers a novel layer of mRNA translation regulation mechanism at codon recognition step mediated by tRNA modification and reveals the critical function of tRNA modification in cancer progression.
2024-03-13 | GSE169589 | GEO
Project description:The RNA methyltransferase METTL1 catalyzes the N7-methylguanosine (m7G) modification of certain tRNAs, mRNAs, and miRNA precursors. However, the role of METTL1 and its cofactor WDR4 in cancer remains largely unexplored. Here we reveal the oncogenic role of METTL1/WDR4. METTL1 is frequently amplified and overexpressed in cancers and correlates with poor patient survival. METTL1 depletion in human cancer cells causes decreased abundance of m7G-modified tRNAs, altered cell cycle, and inhibits oncogenicity. Strikingly, METTL1/WDR4 overexpression induces oncogenic transformation and carcinogenesis. Mechanistically, we find increased abundance of a subset of m7G-modified tRNAs including tRNA-Arg(TCT), and increased translation of mRNAs enriched in the corresponding AGA codon including cell cycle regulators. Accordingly, expression of tRNA-Arg(TCT) is significantly elevated in many cancer types, correlates with patient survival, and overexpression of this tRNA enhances reporter gene expression and cell transformation. Thus, METTL1/WDR4-mediated m7G tRNA modification drives oncogenic transformation, thereby highlighting METTL1 as a promising cancer therapeutic target.
2020-10-01 | GSE149989 | GEO
Project description:The RNA methyltransferase METTL1 catalyzes the N7-methylguanosine (m7G) modification of certain tRNAs, mRNAs, and miRNA precursors. However, the role of METTL1 and its cofactor WDR4 in cancer remains largely unexplored. Here we reveal the oncogenic role of METTL1/WDR4. METTL1 is frequently amplified and overexpressed in cancers and correlates with poor patient survival. METTL1 depletion in human cancer cells causes decreased abundance of m7G-modified tRNAs, altered cell cycle, and inhibits oncogenicity. Strikingly, METTL1/WDR4 overexpression induces oncogenic transformation and carcinogenesis. Mechanistically, we find increased abundance of a subset of m7G-modified tRNAs including tRNA-Arg(TCT), and increased translation of mRNAs enriched in the corresponding AGA codon including cell cycle regulators. Accordingly, expression of tRNA-Arg(TCT) is significantly elevated in many cancer types, correlates with patient survival, and overexpression of this tRNA enhances reporter gene expression and cell transformation. Thus, METTL1/WDR4-mediated m7G tRNA modification drives oncogenic transformation, thereby highlighting METTL1 as a promising cancer therapeutic target.
2020-10-01 | GSE149970 | GEO
Project description:The RNA methyltransferase METTL1 catalyzes the N7-methylguanosine (m7G) modification of certain tRNAs, mRNAs, and miRNA precursors. However, the role of METTL1 and its cofactor WDR4 in cancer remains largely unexplored. Here we reveal the oncogenic role of METTL1/WDR4. METTL1 is frequently amplified and overexpressed in cancers and correlates with poor patient survival. METTL1 depletion in human cancer cells causes decreased abundance of m7G-modified tRNAs, altered cell cycle, and inhibits oncogenicity. Strikingly, METTL1/WDR4 overexpression induces oncogenic transformation and carcinogenesis. Mechanistically, we find increased abundance of a subset of m7G-modified tRNAs including tRNA-Arg(TCT), and increased translation of mRNAs enriched in the corresponding AGA codon including cell cycle regulators. Accordingly, expression of tRNA-Arg(TCT) is significantly elevated in many cancer types, correlates with patient survival, and overexpression of this tRNA enhances reporter gene expression and cell transformation. Thus, METTL1/WDR4-mediated m7G tRNA modification drives oncogenic transformation, thereby highlighting METTL1 as a promising cancer therapeutic target.
2020-10-01 | GSE149950 | GEO