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The effects of N6-methyladenosine RNA methylation on the nervous system

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Abstract

Epitranscriptomics, also known as “RNA epigenetics”, is a type of chemical modification that regulates RNA. RNA methylation is a significant discovery after DNA and histone methylation. The dynamic reversible process of m6A involves methyltransferases (writers), m6A binding proteins (readers), as well as demethylases (erasers). We summarized the current research status of m6A RNA methylation in the neural stem cells’ growth, synaptic and axonal function, brain development, learning and memory, neurodegenerative diseases, and glioblastoma. This review aims to provide a theoretical basis for studying the mechanism of m6A methylation and finding its potential therapeutic targets in nervous system diseases.

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Abbreviations

ac4C:

N4-acetylcytidine

AD:

Alzheimer's disease

ADAR1:

Actadenosine deaminases acting on RNA-1

ALKBH5:

AlkB homolog 5

ALKBH9:

AlkB homolog 9

aNSCs:

Adult neural stem cells

CGCs:

Cerebellar granule cells

DRG:

Adult dorsal root ganglion

EGL:

External granular layer

eIF3:

Eukaryotic translation initiation factor-3

f6A:

N6-formyladenosine

FMRP:

Fragment X mental retardation protein

FTO:

Fat mass and obesity-associated protein

GAK:

G-associated kinase

GBM:

Glioblastoma

GSCs:

Glioblastoma stem cells

hm5C:

5-Hydroxymethylcytidine

hm6A:

N6-hydroxymethyladenosine

HNRNPA2B1:

Heterogeneous nuclear ribonucleoproteins A2/B1

HNRNPC:

Heterogeneous ribonucleoprotein-C

IAPs:

Intracisternal A-particles

IGF2BPs:

Insulin-like growth factor 2 mRNA-binding proteins

iPSCs:

Induced pluripotent stem cells

L1:

Long interspersed element-1

lncRNA:

Long non-coding RNA

m1A:

N1-methyladenosine

m5C:

5-Methylcytosine

m6A:

N6-methyladenosine

m6Am :

N6, 2'-O-dimethyladenosine

MALAT1:

Metastasis-associated lung adenocarcinoma transcript 1

METTL14:

Methyltransferase-like 14

METTL16:

Methyltransferase-like protein 16

METTL3:

Methyltransferase-like 3

miRNA:

MicroRNA

mRNA:

Messenger RNA

NADP:

Nicotinamide adenine dinucleotide phosphate

NMD:

Nonsense-mediated mRNA decay

NMDA:

N-Methyl-D-aspartate

NSCs:

Neural stem cells

OPC:

Oligodendrocyte progenitor cells

PD:

Parkinson's disease

PolyA:

Polyadenosinic acid

PRRC2A:

Proline-rich coiled-coil 2A

RBM15:

RNA-binding motif protein 15

rRNA:

Ribosomal RNA

SAH:

S-Adenosyl homocysteine

SAM:

S-Adenosylmethionine

SENP1:

Sentrin/SUMO-specific protease 1

SLC7A11:

Solute carrier 7A11

SME:

Synaptic m6A epitranscriptome

sncRNA:

Small non-coding RNA

SNPC:

Substantia nigra pars compacta

SNPs:

Single nucleotide polymorphisms

SUMO1:

Small ubiquitin-like modifier 1

SVZ:

Subventricular area

TBI:

Traumatic brain injury

tRNA:

Transfer RNA

WTAP:

Wilms tumor 1-associating protein

YTH:

YT521-B homology

ZC3H13:

Zinc finger CCCH-type containing 13

ZCCHC4:

CCHC zinc finger-containing protein

Ψ :

Pseudouridine

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Funding

This study was supported by the National Natural Science Foundation of China (81873351), and the Distinguished Young Scholars Project of Natural Science Foundation of Anhui Province in China (1908085J27).

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  1. Nan Shao and Ting Ye have authors contributed equally to this work.

Authors and Affiliations

  1. College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230012, China

    Nan Shao, Ting Ye, Meng Zhang, Qian Chen, Peng Zhou, Hang Song & Biao Cai

  2. Department of Neurosurgery (Rehabilitation), Anhui Hospital of Integrated Chinese and Western Medicine, Hefei, 230031, China

    Weiting Xuan

  3. Department of Chinese Internal Medicine, Taihe County People’s Hospital, Fuyang, 236699, China

    Juan Liu

  4. Institute of Integrated Chinese and Western Medicine, Anhui Academy of Chinese Medicine, Hefei, 230012, China

    Peng Zhou, Hang Song & Biao Cai

  5. Key Laboratory of Xin’an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, 230012, China

    Peng Zhou, Hang Song & Biao Cai

  6. Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei, 230012, China

    Peng Zhou, Hang Song & Biao Cai

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  1. Nan Shao
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Nan Shao and Ting Ye analyzed the literature and drafted the manuscript. Weiting Xuan, Meng Zhang, Qian Chen and Liu Juan collected and screened the literature. Peng Zhou, Hang Song and Biao Cai conceived the study and revised the manuscript. All authors read and approved the final manuscript.

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Shao, N., Ye, T., Xuan, W. et al. The effects of N6-methyladenosine RNA methylation on the nervous system. Mol Cell Biochem 478, 2657–2669 (2023). https://doi.org/10.1007/s11010-023-04691-6

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