Functional Dissection of the m6A RNA Modification

Huisman, Brooke D.; Manske, Gabriel L.; Carney, Stephen V.; Kalantry, Sundeep

doi:10.1016/j.tibs.2016.12.004

Cited by 28 publications

(21 citation statements)

References 19 publications

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“…Our results are consistent with previous findings that m6A methylation facilitates mRNA triaging to stress granules (Anders et al, 2018). In contrast to the static m6A modification (Cao et al, 2016;Huisman et al, 2017;Tong et al, 2018), we found that the METTL3-mediated SG formation is dynamic. Identification of the target of METTL3 is an important next step to explore the regulation mechanisms of SG formation.…”

Section: Discussionsupporting

confidence: 93%

Methyltransferase 3 Mediated miRNA m6A Methylation Promotes Stress Granule Formation in the Early Stage of Acute Ischemic Stroke

et al. 2020

Front. Mol. Neurosci.

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The modification of methyltransferase-like (METTL) enzymes plays important roles in various cellular responses by regulating microRNA expression. However, how m6A modification is involved in stress granule (SG) formation in the early stage of acute ischemic stroke by affecting the biogenesis processing of microRNAs remains unclear. Here, we established a middle cerebral artery occlusion (MCAO) model in rats and an oxygen-glucose deprivation/reperfusion (OGD/R) model in primary cortical neurons and PC12 cells to explore the potential mechanism between m6A modification and SG formation. The in vivo results showed that the level of infarction and apoptosis increased while SG formation decreased significantly within the ischemic cortex with improved reperfusion time after 2 h of ischemia. Consistent with the in vivo data, an inverse association between the apoptosis level and SG formation was observed in PC12 cells during the reperfusion period after 6 h of OGD stimulation. Both in vivo and in vitro results showed that the expression of METTL3 protein, m6A and miR-335 was significantly decreased with the reperfusion period. Overexpression of the METTL3 and METTL3 gene-knockdown in PC12 cells were achieved via plasmid transfection and CRISPR-Cas9 technology, respectively. Overexpression or knockdown of METTL3 in oxygen-glucose deprivation of PC12 cells resulted in functional maturation of miR-335, SG formation and apoptosis levels. In addition, we found that miR-335 enhanced SG formation through degradation of the mRNA of the eukaryotic translation termination factor (Erf1). In conclusion, we found that METTL3-mediated m6A methylation increases the maturation of miR-335, which promotes SG formation and reduces the apoptosis level of injury neurons and cells, and provides a potential therapeutic strategy for AIS.

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Section: Discussionsupporting

confidence: 93%

Methyltransferase 3 Mediated miRNA m6A Methylation Promotes Stress Granule Formation in the Early Stage of Acute Ischemic Stroke

et al. 2020

Front. Mol. Neurosci.

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“…Importantly, our findings are not only applicable to RNA structure, but also to the field of RNA modifications. RNA modifications are known to alter the structure, function and activity of RNA molecules [42][43][44][45][46][47][48] . Recent papers have analyzed multiple RNA-Seq datasets looking for mismatched nucleotide signatures, finding that many RNA sequences contain modified nucleosides, 29,30,49 , and in the last year, genome-wide maps identifying thousands of m 1 A modifications have been made available 50 .…”

Section: Discussionmentioning

confidence: 99%

Best practices for genome-wide RNA structure analysis: combination of mutational profiles and drop-off information

Novoa

Beaudoin

Giráldez

et al. 2017

Preprint

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Genome-wide RNA structure maps have recently become available through the coupling of in vivo chemical probing reagents with next-generation sequencing. Initial analyses relied on the identification of truncated reverse transcription reads to identify the chemically modified nucleotides, but recent studies have shown that mutational signatures can also be used.While these two methods have been employed interchangeably, here we show that they actually provide complementary information. Consequently, analyses using exclusively one of the two methodologies may disregard a significant portion of the structural information. We find that the identity and sequence environment of the modified nucleotide greatly affects the odds of introducing a mismatch or causing reverse transcriptase drop-off. Finally, we identify specific mismatch signatures generated by dimethyl sulfate probing that can be used to remove false positives typically produced in RNA structurome analyses, and how these signatures vary depending on the reverse transcription enzyme used.

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“…N6-methyladenosine (m6A) methylation is the most common type of RNA modification that mainly occurs in the messenger RNA (mRNA) of eukaryotes (Huisman et al, 2017). The dynamic modification of m6A is regulated by "writers" (methyltransferases), "readers" (binding proteins), and "erasers" (demethylases) (Yang et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Expression of m6A Regulators Correlated With Immune Microenvironment Predicts Therapeutic Efficacy and Prognosis in Gliomas

Tang

Dai

et al. 2020

Front. Cell Dev. Biol.

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Functional Dissection of the m6A RNA Modification

Cited by 28 publications

References 19 publications

Methyltransferase 3 Mediated miRNA m6A Methylation Promotes Stress Granule Formation in the Early Stage of Acute Ischemic Stroke

Methyltransferase 3 Mediated miRNA m6A Methylation Promotes Stress Granule Formation in the Early Stage of Acute Ischemic Stroke

Best practices for genome-wide RNA structure analysis: combination of mutational profiles and drop-off information

Expression of m6A Regulators Correlated With Immune Microenvironment Predicts Therapeutic Efficacy and Prognosis in Gliomas

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