Inhibition of 6-methyladenine formation decreases the translation efficiency of dihydrofolate reductase transcripts

Tuck, Martin T.; Wiehl, Paul E.; Pan, Tao

doi:10.1016/s1357-2725(99)00041-2

Cited by 36 publications

(30 citation statements)

References 27 publications

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“…A 1.5-fold increase was detected when comparing the translation level of methylated transcripts to that of unmethylated transcripts [88]. Similarly, when cytoplasmic transcripts purified from cycloleucine-treated cells were in vitro translated, the amount of DHFR protein produced from undermethylated mRNA was 20% less than untreated mRNA [89]. Although cycloleucine can inhibit both 2′- O -methylation and m 6 A methylation, 2′- O -methylation normally plays a negative effect on protein translation; therefore the observed enhancement of translation after cycloleucine treatment should be caused solely by m 6 A modification.…”

Section: Effect Of M6a On Rna Metabolismmentioning

confidence: 94%

N6-Methyl-Adenosine (m6A) in RNA: An Old Modification with A Novel Epigenetic Function

Niu

Yong-sheng

et al. 2012

Genomics, Proteomics &Amp; Bioinformatics

389

305

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N6-methyl-adenosine (m6A) is one of the most common and abundant modifications on RNA molecules present in eukaryotes. However, the biological significance of m6A methylation remains largely unknown. Several independent lines of evidence suggest that the dynamic regulation of m6A may have a profound impact on gene expression regulation. The m6A modification is catalyzed by an unidentified methyltransferase complex containing at least one subunit methyltransferase like 3 (METTL3). m6A modification on messenger RNAs (mRNAs) mainly occurs in the exonic regions and 3′-untranslated region (3′-UTR) as revealed by high-throughput m6A-seq. One significant advance in m6A research is the recent discovery of the first two m6A RNA demethylases fat mass and obesity-associated (FTO) gene and ALKBH5, which catalyze m6A demethylation in an α-ketoglutarate (α-KG)- and Fe2+-dependent manner. Recent studies in model organisms demonstrate that METTL3, FTO and ALKBH5 play important roles in many biological processes, ranging from development and metabolism to fertility. Moreover, perturbation of activities of these enzymes leads to the disturbed expression of thousands of genes at the cellular level, implicating a regulatory role of m6A in RNA metabolism. Given the vital roles of DNA and histone methylations in epigenetic regulation of basic life processes in mammals, the dynamic and reversible chemical m6A modification on RNA may also serve as a novel epigenetic marker of profound biological significances.

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Section: Effect Of M6a On Rna Metabolismmentioning

confidence: 94%

N6-Methyl-Adenosine (m6A) in RNA: An Old Modification with A Novel Epigenetic Function

Niu

Yong-sheng

et al. 2012

Genomics, Proteomics &Amp; Bioinformatics

389

305

View full text Add to dashboard Cite

show abstract

“…m 6 A was also shown to be enriched around the stop codon of RNA transcripts and conserved between people and mouse [6, 7], implicating a potential role played by m 6 A in post-transcriptional regulation [6, 8, 9]. Since then, m 6 A has been shown to have a number of important biological functions, including promoting RNA degradation [10], regulating RNA stability by modulating binding of RNA binding proteins [6, 11, 12], and controlling translation efficiency [13–17]. Meanwhile, the identification of m 6 A methyltransferases and demethylases [4, 18–20] further revealed the regulators of epitranscriptome.…”

Section: Introductionmentioning

confidence: 99%

“…Then, a DmM functional network is constructed for each RS by searching the significant interactions with DmMGs in PPI network using a Random Walk with Restart (RWR) algorithm. We adopt PPI network here to model functional interactions of m 6 A mediating genes because m 6 A has been shown to regulate the process of translation [13–17], in addition to its influence on gene expression. Finally, a consensus m 6 A-driven gene network is built by taking all the significant reoccurring interactions.…”

Section: Introductionmentioning

confidence: 99%

m6A-Driver: Identifying Context-Specific mRNA m6A Methylation-Driven Gene Interaction Networks

Zhang

Meng

et al. 2016

PLoS Comput Biol

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As the most prevalent mammalian mRNA epigenetic modification, N6-methyladenosine (m6A) has been shown to possess important post-transcriptional regulatory functions. However, the regulatory mechanisms and functional circuits of m6A are still largely elusive. To help unveil the regulatory circuitry mediated by mRNA m6A methylation, we develop here m6A-Driver, an algorithm for predicting m6A-driven genes and associated networks, whose functional interactions are likely to be actively modulated by m6A methylation under a specific condition. Specifically, m6A-Driver integrates the PPI network and the predicted differential m6A methylation sites from methylated RNA immunoprecipitation sequencing (MeRIP-Seq) data using a Random Walk with Restart (RWR) algorithm and then builds a consensus m6A-driven network of m6A-driven genes. To evaluate the performance, we applied m6A-Driver to build the context-specific m6A-driven networks for 4 known m6A (de)methylases, i.e., FTO, METTL3, METTL14 and WTAP. Our results suggest that m6A-Driver can robustly and efficiently identify m6A-driven genes that are functionally more enriched and associated with higher degree of differential expression than differential m6A methylated genes. Pathway analysis of the constructed context-specific m6A-driven gene networks further revealed the regulatory circuitry underlying the dynamic interplays between the methyltransferases and demethylase at the epitranscriptomic layer of gene regulation.

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“…Of special interest is the m6A modification, which is the main substrate of methylation in mRNA. This modification has been suggested to affect RNA processing [13]–[15], RNA transport [16]–[18] and translation efficiency [19]. m6A RNA methylation is catalysed by methyltransferases (METTL14 and METTL3) in association with the splicing factor WTAP [20], [21].…”

Section: Introductionmentioning

confidence: 99%

Changes in Gene Expression Associated with FTO Overexpression in Mice

et al. 2014

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Single nucleotide polymorphisms in the first intron of the fat-mass-and-obesity-related gene FTO are associated with increased body weight and adiposity. Increased expression of FTO is likely underlying this obesity phenotype, as mice with two additional copies of Fto (FTO-4 mice) exhibit increased adiposity and are hyperphagic. FTO is a demethylase of single stranded DNA and RNA, and one of its targets is the m6A modification in RNA, which might play a role in the regulation of gene expression. In this study, we aimed to examine the changes in gene expression that occur in FTO-4 mice in order to gain more insight into the underlying mechanisms by which FTO influences body weight and adiposity. Our results indicate an upregulation of anabolic pathways and a downregulation of catabolic pathways in FTO-4 mice. Interestingly, although genes involved in methylation were differentially regulated in skeletal muscle of FTO-4 mice, no effect of FTO overexpression on m6A methylation of total mRNA was detected.

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Inhibition of 6-methyladenine formation decreases the translation efficiency of dihydrofolate reductase transcripts

Cited by 36 publications

References 27 publications

N6-Methyl-Adenosine (m6A) in RNA: An Old Modification with A Novel Epigenetic Function

N6-Methyl-Adenosine (m6A) in RNA: An Old Modification with A Novel Epigenetic Function

m6A-Driver: Identifying Context-Specific mRNA m6A Methylation-Driven Gene Interaction Networks

Changes in Gene Expression Associated with FTO Overexpression in Mice

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