Down-Regulation of m6A mRNA Methylation Is Involved in Dopaminergic Neuronal Death

ACS Chemical Neuroscience, Journal Year: 2019, Volume and Issue: 10(5), P. 2355 - 2363

Published: March 5, 2019

N6-Methyladenosine (m6A) is the most prevalent internal modification that occurs in mRNA of eukaryotes and plays a vital role post-transcriptional regulation. Recent studies highlighted biological significance m6A nervous system, its dysregulation has been shown to be related degenerative neurodevelopmental diseases. Parkinson's disease (PD) common age-related neurological disorder with pathogenesis still not fully elucidated. Reports have epigenetic mechanisms including DNA methylation histone acetylation, which alter gene expression, are associated PD. In this study, we found global mRNAs down-regulated 6-OHDA-induced PC12 cells striatum PD rat brain. To further explore relationship between molecular mechanism PD, decreased dopaminergic by overexpressing nucleic acid demethylase, FTO, or inhibitor. The results showed reduction could induce expression N-methyl-d-aspartate (NMDA) receptor 1, elevate oxidative stress Ca2+ influx, resulting neuron apoptosis. Collectively, may play death neuron, provides novel view understand regulation disease.

Language: Английский

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Crosstalk between epitranscriptomic and epigenetic mechanisms in gene regulation

Trends in Genetics, Journal Year: 2021, Volume and Issue: 38(2), P. 182 - 193

Published: July 19, 2021

Chemical modifications on histones, DNA, and RNA robustly impact gene regulation. Installation of the modification m6A leads to altered mRNA stability translation. Emerging data suggest that perturbations in feedback epigenetic checkpoints vice versa.RNA methylation intracisternal A particle, a type repetitive element, is required for proper heterochromatin formation maintain genome integrity.Loss mouse embryonic stem cells enhances chromatin-associated RNAs, leading more-open chromatin active transcription.m6A destabilizes transcripts encode histone-modifying enzymes complexes, including KDM6B, CBP, P300.The histone elongation mark H3K36me3 guides deposition.Xist-mediated silencing X chromosome requires deposition recognition by reader proteins.m6A influence extends beyond stability, investigation functional effects biogenesis should be considered physiological mechanistic studies. Epigenetic occur genomic DNA histones expression. More recently, discovery undergoes similar chemical powerfully transcript turnover translation adds another layer dynamic Central precise synchronized regulation expression intricate crosstalk between multiple involved biosynthesis processing. There are more than 100 internal mammalian cells. The most common N6-methyladenosine (m6A) methylation. Although established dynamics efficiency, rapidly accumulating evidence shows significant histone/DNA mechanisms. These interactions specify transcriptional outputs, translation, recruitment modifiers, as well deployment methyltransferase complex (MTC) at target sites. In this review, we dissect m6A-orchestrated circuits regulate activity regulatory such long noncoding (lnc)RNA chromosome-associated RNA. Collectively, body suggests acts versatile checkpoint can couple different layers with one another.

Language: Английский

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The RNA Methyltransferase NSUN2 and Its Potential Roles in Cancer

Cells, Journal Year: 2020, Volume and Issue: 9(8), P. 1758 - 1758

Published: July 22, 2020

5-methylcytosine is often associated as an epigenetic modifier in DNA. However, it also found increasingly a plethora of RNA species, predominantly transfer RNAs, but cytoplasmic and mitochondrial ribosomal enhancer number long noncoding RNAs. Moreover, this modification can be messenger RNAs has led to increasing appreciation that methylation functionally regulate gene expression cellular activities. In mammalian cells, the addition m5C cytosines carried out by enzymes NOL1/NOP2/SUN domain (NSUN) family well DNA methyltransferase homologue DNMT2. regard, NSUN2 critical for adding mRNA. review, using non-small cell lung cancer other cancers primary examples, we discuss recent developments known functions its potential role cancer.

Language: Английский

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Altered m6A Modification of Specific Cellular Transcripts Affects Flaviviridae Infection

Molecular Cell, Journal Year: 2019, Volume and Issue: 77(3), P. 542 - 555.e8

Published: Dec. 3, 2019

Language: Английский

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Naturally occurring modified ribonucleosides

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2020, Volume and Issue: 11(5)

Published: April 16, 2020

The chemical identity of RNA molecules beyond the four standard ribonucleosides has fascinated scientists since pseudouridine was characterized as "fifth" ribonucleotide in 1951. Since then, ever-increasing number and complexity modified have been found viruses throughout all three domains life. Such modifications can be simple methylations, hydroxylations, or thiolations, complex ring closures, glycosylations, acylations, aminoacylations, unusual incorporation selenium. While initially transfer ribosomal RNAs, also exist messenger RNAs noncoding RNAs. Modifications profound cellular outcomes at various levels, such altering structure being essential for cell survival organism viability. aberrant presence absence lead to human disease, ranging from cancer metabolic developmental illnesses Hoyeraal-Hreidarsson syndrome, Bowen-Conradi Williams-Beuren syndrome. In this review article, we summarize characterization 143 currently known by describing their taxonomic distributions, enzymes that generate modifications, any implications processes, structure, disease. We highlight areas active research, specific contain a particular type modification well methodologies used identify novel modifications. This article is categorized under: Processing > Editing Modification.

Language: Английский

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