Naturally occurring modified ribonucleosides DOI Creative Commons
Phillip J. McCown, Agnieszka Ruszkowska, Charlotte N. Kunkler

et al.

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

The m6A epitranscriptome: transcriptome plasticity in brain development and function DOI
Ido Livneh, Sharon Moshitch-Moshkovitz, Ninette Amariglio

et al.

Nature reviews. Neuroscience, Journal Year: 2019, Volume and Issue: 21(1), P. 36 - 51

Published: Dec. 5, 2019

Language: Английский

Citations

257
The RNA m6A reader YTHDC1 silences retrotransposons and guards ES cell identity DOI
Jiadong Liu, Mingwei Gao, Jiangping He

et al.

Nature, Journal Year: 2021, Volume and Issue: 591(7849), P. 322 - 326

Published: March 3, 2021

Language: Английский

Citations

254
Landscape and Regulation of m6A and m6Am Methylome across Human and Mouse Tissues DOI Creative Commons
June Liu, Kai Li, Jia‐Bin Cai

et al.

Molecular Cell, Journal Year: 2019, Volume and Issue: 77(2), P. 426 - 440.e6

Published: Oct. 30, 2019

Language: Английский

Citations

237
Biological roles of adenine methylation in RNA DOI
Konstantinos Boulias, Eric Lieberman Greer

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 24(3), P. 143 - 160

Published: Oct. 19, 2022

Language: Английский

Citations

212
The N6-methyladenosine (m6A)-forming enzyme METTL3 facilitates M1 macrophage polarization through the methylation of STAT1 mRNA DOI Open Access
Yihan Liu, Zhujiang Liu, Hao Tang

et al.

AJP Cell Physiology, Journal Year: 2019, Volume and Issue: 317(4), P. C762 - C775

Published: July 31, 2019

Compelling evidence indicates that epigenetic regulations orchestrate dynamic macrophage polarization. N6-methyladenosine (m6A) methylation is the most abundant modification of mammalian mRNA, but its role in polarization still completely unknown. Here, we show m6A-catalytic enzyme methyltransferase like 3 (METTL3) specifically upregulated following M1 mouse macrophages. Furthermore, METTL3 knockdown through siRNA transfection markedly inhibited M1, enhanced M2, Conversely, overexpression via plasmid greatly facilitated attenuated Further methylated RNA immunoprecipitation and vitro m6A assays suggested directly methylates mRNA encoding signal transducer activator transcription 1 (STAT1), a master factor controlling polarization, at coding sequence 3'-untranslated regions. In addition, METTL3-mediated STAT1 significantly increased stability subsequently expression. conclusion, drives by methylating potentially serving as an anti-inflammatory target.

Language: Английский

Citations

211
Context-dependent functional compensation between Ythdf m6A reader proteins DOI Open Access

Lior Lasman,

Vladislav Krupalnik,

Sergey Viukov

et al.

Genes & Development, Journal Year: 2020, Volume and Issue: 34(19-20), P. 1373 - 1391

Published: Sept. 17, 2020

The N6-methyladenosine (m 6 A) modification is the most prevalent post-transcriptional mRNA modification, regulating decay and splicing. It plays a major role during normal development, differentiation, disease progression. regulated by set of writer, eraser, reader proteins. YTH domain family proteins consists three homologous m A-binding proteins, Ythdf1, Ythdf2, Ythdf3, which were suggested to have different cellular functions. However, their sequence similarity tendency bind same targets suggest that they may overlapping roles. We systematically knocked out (KO) Mettl3 each Ythdf readers, readers together (triple-KO). then estimated effect in vivo mouse gametogenesis, postnatal viability, vitro embryonic stem cells (mESCs). In Mettl3-KO severity increased as deletion occurs earlier process, Ythdf2 has dominant cannot be compensated Ythdf1 or due differences readers’ expression pattern across cell types, both quantity spatial location. Knocking testing viable offspring genotypes revealed redundancy early development Ythdf1/2/3 gene dosage-dependent. Finally, mESCs there compensation between since resistance differentiate significant on occur only triple-KO not single KOs. Thus, we new model for function, profound dosage-dependent when all are equivalently coexpressed types.

Language: Английский

Citations

201
N6-methyladenosine dynamics in neurodevelopment and aging, and its potential role in Alzheimer’s disease DOI Creative Commons
Andrew M. Shafik, Feiran Zhang, Zhenxing Guo

et al.

Genome biology, Journal Year: 2021, Volume and Issue: 22(1)

Published: Jan. 5, 2021

N6-methyladenosine (m

Citations

196
Leukemogenic Chromatin Alterations Promote AML Leukemia Stem Cells via a KDM4C-ALKBH5-AXL Signaling Axis DOI Creative Commons
Jiazhen Wang, Yicun Li, Peipei Wang

et al.

Cell stem cell, Journal Year: 2020, Volume and Issue: 27(1), P. 81 - 97.e8

Published: May 12, 2020

Language: Английский

Citations

195
Hidden codes in mRNA: Control of gene expression by m6A DOI Creative Commons

Shino Murakami,

Samie Jaffrey

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(12), P. 2236 - 2251

Published: June 1, 2022

Language: Английский

Citations

190
N6-methyladenosine modification regulates ferroptosis through autophagy signaling pathway in hepatic stellate cells DOI Creative Commons
Min Shen, Yujia Li, Yingqian Wang

et al.

Redox Biology, Journal Year: 2021, Volume and Issue: 47, P. 102151 - 102151

Published: Sept. 27, 2021

Ferroptosis is a recently identified non-apoptotic form of cell death characterized by iron-dependent lipid peroxidation. However, the underlying exact mechanisms remain poorly understood. Here, we report that total levels N6-methyladenosine (m6A) modification are evidently increased upon exposure to ferroptosis-inducing compounds due upregulation methylase METTL4 and downregulation demethylase FTO. Interestingly, RNA-seq shows m6A appears trigger autophagy activation stabilizing BECN1 mRNA, which may be potential mechanism for modification-enhanced HSC ferroptosis. Importantly, YTHDF1 as key reader protein mRNA stability, knockdown could prevent plasmid-induced Noteworthy, promotes stability via recognizing binding site within coding regions. In mice, erastin treatment alleviates liver fibrosis inducing HSC-specific inhibition impair erastin-induced ferroptosis in murine fibrosis. Moreover, retrospectively analyzed effect sorafenib on advanced fibrotic patients with hepatocellular carcinoma (HCC) receiving monotherapy. Attractively, upregulation, activation, induction occur human HSCs. Overall, these findings reveal novel signaling pathways molecular ferroptosis, also identify modification-dependent target

Language: Английский

Citations

181