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Review
. 2020 Aug 11:8:782.
doi: 10.3389/fcell.2020.00782. eCollection 2020.

Roles of N6-Methyladenosine (m6A) in Stem Cell Fate Decisions and Early Embryonic Development in Mammals

Meng Zhang  1 , Yanhui Zhai  1 , Sheng Zhang  1 , Xiangpeng Dai  1 , Ziyi Li  1
Affiliations
Review

Roles of N6-Methyladenosine (m6A) in Stem Cell Fate Decisions and Early Embryonic Development in Mammals

Meng Zhang et al. Front Cell Dev Biol. .

Erratum in

Abstract

N6-methyladenosine (m6A) is one of the most abundant internal mRNA modifications, and it affects multiple biological processes related to eukaryotic mRNA. The majority of m6A sites are located in stop codons and 3'UTR regions of mRNAs. m6A regulates RNA metabolism, including alternative splicing (AS), alternative polyadenylation (APA), mRNA export, decay, stabilization, and translation. The m6A metabolic pathway is regulated by a series of m6A writers, erasers and readers. Recent studies indicate that m6A is essential for the regulation of gene expression, tumor formation, stem cell fate, gametogenesis, and animal development. In this systematic review, we summarized the recent advances in newly identified m6A effectors and the effects of m6A on RNA metabolism. Subsequently, we reviewed the functional roles of RNA m6A modification in diverse cellular bioprocesses, such as stem cell fate decisions, cell reprogramming and early embryonic development, and we discussed the potential of m6A modification to be applied to regenerative medicine, disease treatment, organ transplantation, and animal reproduction.

Keywords: N6-methyladenosine; RNA metabolism; cell reprogramming; embryonic development; stem cell fate.

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Figures

FIGURE 1
FIGURE 1
The characteristics of RNA m6A modification. The m6A writers, erasers, and readers in eukaryotic cells (Shi et al., 2019). The preferences and density of RNA m6A modification in different regions of mRNAs (Fitzsimmons and Batista, 2019).
FIGURE 2
FIGURE 2
RNA m6A modifications regulate RNA metabolism. m6A is deposited onto nascent mRNAs by MTC. Then the m6A-modified mRNAs undergo AS by recruiting splicing factors to m6A sites or their flanking sequences. On the other hand, YTHDC1 and VIRMA can interact with the polyadenylation cleavage factors CPSF5 and CPSF6, thus regulating mRNA APA. Then, mRNAs can be recognized by YTHDC1 or FMRP and exported into the cytoplasm. Cytoplasmic m6A readers regulate mRNA stability (IGF2BPs), decay (YTHDF2), and translation (YTHDF1/3, YTHDC2, EIF3a, and METTL3) under normal and stress conditions.
FIGURE 3
FIGURE 3
m6A regulates the pluripotent stem cell fate. METTL3 or m6A deletion has divergent effects on the fate decision of pluripotent stem cells in different states. METTL3 and ZFP217 play divergent roles in somatic cell reprogramming at different stages.
FIGURE 4
FIGURE 4
The crucial roles of m6A in stem cell and progenitor cell differentiation. m6A plays divergent functions by affecting mRNA splicing (•), stability (■), and translation (★). ECs: endothelial cells; HSPCs: hematopoietic stem/progenitor cells; NSCs: neural stem cells; NPCs: neural progenitor cells; SSCs: spermatogonial stem cells; ADSCs: adipose-derived stem cell; and BMSCs: bone marrow mesenchymal stem cells.
FIGURE 5
FIGURE 5
The m6A modification-related proteins exert essential functions in early embryonic development. The highlighted color indicates that the proteins mainly play functions at this stage.
See this image and copyright information in PMC

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