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METTL5, an 18S rRNA-specific m6A methyltransferase, modulates expression of stress response genes

ABSTRACT: METTL5, an 18S rRNA-specific m6A methyltransferase, modulates expression of stress response genes

PROVIDER: PRJNA574637 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10196386_1.fastq.gz	Fastqsanger.gz
	SRR10196386_2.fastq.gz	Fastqsanger.gz
	SRR10196387_1.fastq.gz	Fastqsanger.gz
	SRR10196387_2.fastq.gz	Fastqsanger.gz
	SRR10196388_1.fastq.gz	Fastqsanger.gz

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The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112

Project description:N6-methyladenosine (m6A) has recently been found abundantly on messenger RNA and shown to regulate most steps of mRNA metabolism. Several important m6A methyltransferases have been described functionally and structurally, but the enzymes responsible for installing one m6A residue on each subunit of human ribosomes at functionally important sites have eluded identification for over 30 years. Here we identify METTL5 as the enzyme responsible for 18S rRNA m6A modification and confirm ZCCHC4 as the 28S rRNA modification enzyme. We show that METTL5 must form a heterodimeric complex with TRMT112, a known methyltransferase activator, to gain metabolic stability in cells. We provide the first atomic resolution structure of METTL5-TRMT112, supporting that its RNA binding mode differs distinctly from that of other m6A RNA methyltransferases. On the basis of similarities with a DNA methyltransferase, we propose that METTL5-TRMT112 acts by extruding the adenosine to be modified from a double-stranded nucleic acid.

2019-07-15 | GSE128699 | GEO

METTL5, an 18S rRNA-specific m6A methyltransferase, regulates the Integrated Stress Response [eCLIP]

Project description:RNA N6-methyladenosine (m6A) modification is present in different RNA molecules, including protein-coding mRNAs and non-coding RNAs such as ribosomal RNAs (rRNAs).Here, we report that mammalian METTL5, a member of a highly conserved methyltransferase family, specifically methylates adenosine 1832 (A1832) in the 18S rRNA in vivo and in vitro.

2020-09-17 | GSE138123 | GEO

The rRNA m6A methyltransferase METTL5 is involved in pluripotency and developmental programmes

Project description:Covalent chemical modifications of cellular RNAs directly impact all biological processes. However, our mechanistic understanding of the enzymes catalysing these modifications, their substrates and biological functions remains vague. Here, we undertook a systematic screen to uncover new RNA methyltransferases. We demonstrate that the methyltransferase-like 5 (METTL5) protein catalyses m6A in 18S rRNA at position A1832. We report that absence of Mettl5 in mouse embryonic stem cells (mESCs) results in a changes gene expression, decrease in translation rate, spontaneous loss of pluripotency and compromised differentiation potential. Mice lacking METTL5 recapitulate symptoms of patients with METTL5 mutations, thereby providing a new mouse disease model. Overall, our work highlights the importance of m6A in rRNA in stemness, differentiation, development and diseases.

2020-04-15 | GSE144346 | GEO

The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112

Project description:The human 18S rRNA m6A methyltransferase METTL5 is stabilized by TRMT112

| PRJNA528519 | ENA

Methyltransferase METTL5 interactome

Project description:Cellular RNAs are covalently modified and these modifications can impact on all biological processes and hence are implicated in different types of diseases. Amongst RNA modifications, N6-methyladenosine (m6A) is one of the most widespread and has been found on messenger (mRNA), ribosomal (rRNA), non-coding and spliceosomal RNAs. We undertook a systematic screen to uncover new RNA-methyltransferases. We demonstrate that the methyltransferase-like 5 protein (METTL5) is an 18S rRNA specific methyltransferase and interacts specifically with Trmt122.

2020-09-09 | PXD015582 | Pride

The 18S rRNA m6A methyltransferase METTL5 promotes mouse embryonic stem cell differentiation

Project description:The 18S rRNA m6A methyltransferase METTL5 promotes mouse embryonic stem cell differentiation

| PRJNA575537 | ENA

METTL5, an 18S rRNA-specific m6A methyltransferase, modulates expression of stress response genes

Project description:Input mRNAs and ribosome protected fragments (RPFs) from wildtype and Mettl5 knockout (KO) B16 cells were analyzed by TruSeq Ribo Profile (Illumina) library preparation and high throughput sequencing

2020-04-28 | GSE138110 | GEO

Function and Mechanism of METTL5-mediated 18S rRNA m6A1832 modification in hepatocellular carcinoma

Project description:Tumor recurrence is main pattern of treatment failure for early-stage hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying disease recurrence remain poorly understood. Here, we showed that 18S rRNA N6-methyladenosine (m6A1832) modification and its methyltransferase complex METTL5/TRMT112 were upregulated in HCC and correlated with poor prognosis. Loss-of-function and gain-of-function assays demonstrated that METTL5/TRMT112 mediated 18S rRNA m6A1832 modification promotes HCC tumorigenesis in vitro and in vivo. Mechanistically, 18S rRNA m6A1832 modification selectively regulated the translation of mRNAs with long 5’UTR and short 3’UTR through affecting the assembly of 80S subunit at translation initiation and its dissociation at translation termination which was executed by weakening the interaction of ABCE1 with eRF1 and eRF3. Moreover, METTL5-mediated 18S rRNA m6A1832 modification regulated β-oxidation of long-chain fatty acid through ACSL4 to promote HCC progression. Our work uncovered a novel layer of mRNA translation regulation mechanism at ribosome 80S subunit assembly and dissociation step mediated by 18S rRNA m6A1832 modification and revealed a new crosslink between RNA epigenetic modification and fatty acid metabolism in HCC.

2021-06-01 | GSE175827 | GEO

METTL5, an 18S rRNA-specific m6A methyltransferase, regulates the Integrated Stress Response [eCLIP]

Project description:METTL5, an 18S rRNA-specific m6A methyltransferase, regulates the Integrated Stress Response [eCLIP]

| PRJNA574656 | ENA

Loss of m6A methyltransferase METTL5 promotes cardiac hypertrophy through translational control of SUZ12

Project description:The methyltransferase-like5 (METTL5), which catalyzes m6A in 18S rRNA at position A1832, has been shown to regulate the efficient of mRNA translation in the differentiation of ES cell and the growth of cancer cells. It remains unknown that whether and how METTL5 regulates cardiac hypertrophy. In this study, we generated a mouse model (METTL5-cKO) with cardiac-specific abolishment of METTL5 in vivo. Loss function of METTL5 promotes pressure overload-induced cardiomyocyte hypertrophy and adverse remodeling. The regulatory function of METTL5 in hypertrophic growth of cardiomyocyte were further confirmed with both gain- and loss-of-function approaches in primary isolated cardiomyocytes. Mechanically, METTL5 was identified to modulate the mRNA translation of SUZ12, a core component of PRC2 complex, and further regulate the transcriptome shift during cardiac hypertrophy. Therefore, our study uncover an important translational regulator of cardiac hypertrophy.

2022-02-13 | GSE186615 | GEO

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