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N1-methyladenosine methylations in tRNA drive liver tumorigenesis by PPARδ-mediated cholesterol synthesis

ABSTRACT: N1-methyladenosine methylations in tRNA drive liver tumorigenesis by PPARδ-mediated cholesterol synthesis

PROVIDER: PRJNA622261 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11459631.fastq.gz	Fastqsanger.gz
	SRR11459632.fastq.gz	Fastqsanger.gz
	SRR11459633.fastq.gz	Fastqsanger.gz
	SRR11459634.fastq.gz	Fastqsanger.gz
	SRR11459635.fastq.gz	Fastqsanger.gz

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N1-methyladenosine methylations in tRNA drive liver tumorigenesis by PPARδ-mediated cholesterol synthesis

Project description:Increased protein translation plays a critical role in cancer development and treatment1,2. However, the molecular mechanism that is involved in this process remains poorly understood. N1-methyladenosine (m1A) methylation in RNA accounts for regulating mRNA translation in a post-transcriptional manner3,4. Here we show that m1A methylation levels are remarkably elevated in hepatocellular carcinoma (HCC) patient tumor tissues, especially in patients with microscopic vascular invasion (MVI). Moreover, m1A methylation signals are increased in liver cancer stem cells (CSCs) and are negatively correlated with HCC patient survival. Consistently, TRMT6 and TRMT61A, forming m1A methyltransferase complex, are highly expressed in advanced HCC tumors and are negatively correlated with HCC survival. TRMT6/TRMT61A-mediated m1A methylations are required for self-renewal of liver CSCs and tumorigenesis. Mechanistically, TRMT6/TRMT61A-dependent m1A in tRNA boost PPARδ expression, which triggers cholesterol synthesis to activate Hedgehog signaling, driving self-renewal of liver CSCs and tumorigenesis. For potential therapeutic benefit, we further identify a specific inhibitor against TRMT6/TRMT61A complex that exerts effective therapeutic effect on liver cancer with high m1A methylations. Our findings provide novel insights into the function and molecular mechanism of m1A modifications underlying liver tumorigenesis and drug target, which will serve as a new biomarker for HCC and pave a new way to develop more effective therapeutic strategies for HCC patients.

2021-03-01 | GSE147840 | GEO

Analysis of N1-methyladenosine methylome (m1A) enrichment level in ocular melanoma.

Project description:To investigate the function of N1-methyladenosine methylome (m1A) in ocular melanoma, we analyzed m1A enrichment level in ocular melanoma and melanocyte cell lines and established ALKBH3 knock down cell lines in 92.1.

2022-09-22 | GSE213748 | GEO

N1-methyladenosine methylome in messenger RNA in petunia

Project description:N1-methyladenosine methylome in messenger RNA in petunia

| PRJNA564045 | ENA

Transcriptome-wide mapping reveals reversible and dynamic N1-methyladenosine methylome

Project description:N1-Methyladenosine (m1A) is a prevalent post-transcriptional RNA modification, yet little is known about its abundance, topol- ogy and dynamics in mRNA. Here, we show that m1A is prevalent in Homo sapiens mRNA, which shows an m1A/A ratio of ~0.02%. We develop the m1A-ID-seq technique, based on m1A immunoprecipitation and the inherent ability of m1A to stall reverse tran- scription, as a means for transcriptome-wide m1A profiling. m1A-ID-seq identifies 901 m1A peaks (from 600 genes) in mRNA and noncoding RNA and reveals a prominent feature, enrichment in the 5' untranslated region of mRNA transcripts, that is dis- tinct from the pattern for N6-methyladenosine, the most abundant internal mammalian mRNA modification. Moreover, m1A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase. Lastly, we show that m1A methylation responds dynamically to stimuli, and we identify hundreds of stress-induced m1A sites. Collectively, our approaches allow comprehensive analysis of m1A modification and provide tools for functional studies of potential epigenetic regulation via the reversible and dynamic m1A methylation.

2016-02-05 | GSE73941 | GEO

Evolution of a Reverse Transcriptase to Map N1-Methyladenosine in Human mRNA

Project description:Chemical modifications on mRNA are increasingly recognized as a critical regulatory layer of the flow of genetic information, but quantitative tools to monitor RNA modifications in a whole-transcriptome and site-specific manner are lacking. Here we describe a versatile directed evolution platform that rapidly selects for reverse transcriptases that install mutations during reverse transcription at sites of a given type of RNA modification, allowing for site-specific identification of the modification. To develop and validate the platform, we evolved the HIV-1 reverse transcriptase against N1-methyladenosine (m1A). Iterative rounds of selection yielded reverse transcriptases with both robust read-through and high mutation rates at m1A sites. We apply the evolved reverse transcriptase to identify thousands of statistically confident m1A sites in human mRNA, some of which can be detected in antibody-free RNA-seq libraries. Together, this work develops and validates the reverse transcriptase evolution platform and provides new tools, analysis methods, and datasets to study m1A biology.

2019-09-24 | GSE123365 | GEO

N1-methyladenosine methylome in messenger RNA in petunia

Project description:N1-methyladenosine is a unique base methylation because it blocks Watson-Crick base paring and introduces a positive charge. Previous studies showed that m1A is prevalent in yeast and mammals mRNA and has a functional role in promoting translation of methylated mRNA. However, little is known about its abundance, topology and dynamics in plant mRNA. In this study, dot blotting and LC–MS/MS analyses reveal a dynamic pattern of m1A mRNA modification in various tissues and at different developmental stages in petunia (Petunia hybrida). Transcriptome-wide profiling of mRNA m1A in petunia was reported by applying m1A mRNA immunoprecipitation followed by a deep-sequencing approach (m1A-seq). m1A-seq analysis identified 4993 m1A peaks in 3231 expressed genes in petunia corollas. Each methylated gene averagely carries 1.55 peaks. Among the identified m1A peaks, there are 251 m1A peaks in which the adenines was partly replaced by thymine (T) and/or the reverse transcription stops happened in adenine site, in 199 expressed genes. We found that m1A is enriched in coding sequences with one peaks located immediately after start codons, and a slight negative correlation between methylated genes and gene expression was observed. Totally, ethylene treatment reduced the m1A level of mRNA in petunia corollas. We show that a RNA m1A-methyltransferase, tRNA specific methyltransferase 61A (PhTRMT61A), is an m1A mRNA methyltransferase. PhTRMT61A silencing results in decreased m1A peaks in mRNA in leaves and abnormal leaf development. PhTRMT61A is located to the nucleus. Our results suggest that m1A in mRNA is an important epitranscriptome marker and plays a role in plant development.

2020-08-12 | GSE136921 | GEO

Analysis of N1-methyladenosine methylome (m1A) enrichment level in ocular melanoma.

Project description:Analysis of N1-methyladenosine methylome (m1A) enrichment level in ocular melanoma.

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N1-methyladenosine modification in mitochondrial tRNAs is associated with Alzheimer’s disease

Project description:N1-methyladenosine modification in mitochondrial tRNAs is associated with Alzheimer’s disease

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

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

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Evolution of a Reverse Transcriptase to Map N1-Methyladenosine in Human mRNA

Project description:Evolution of a Reverse Transcriptase to Map N1-Methyladenosine in Human mRNA