Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Oct:46:77-82.
doi: 10.1016/j.gde.2017.06.006. Epub 2017 Jul 3.

The N6-Methyladenosine RNA modification in pluripotency and reprogramming

Francesca Aguilo  1 , Martin J Walsh  2
Affiliations
Review

The N6-Methyladenosine RNA modification in pluripotency and reprogramming

Francesca Aguilo et al. Curr Opin Genet Dev. 2017 Oct.

Abstract

Chemical modifications of RNA provide a direct and rapid way to manipulate the existing transcriptome, allowing rapid responses to the changing environment further enriching the regulatory capacity of RNA. N6-Methyladenosine (m6A) has been identified as the most abundant internal modification of messenger RNA in eukaryotes, linking external stimuli to an intricate network of transcriptional, post-transcriptional and translational processes. M6A modification affects a broad spectrum of cellular functions, including maintenance of the pluripotency of embryonic stem cells (ESCs) and the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). In this review, we summarize the most recent findings on m6A modification with special focus on the different studies describing how m6A is implicated in ESC self-renewal, cell fate specification and iPSC generation.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Scheme of m6A reversible methylation and mediated functions
Dynamic m6A modification is regulated by writers (METTL3, METTL14 and WTAP) and erasers (FTO and ALKBH5). Recognition of m6A by different readers in the nucleus or the cytoplasm mediates divergent functions, including splicing, pri-miRNA processing, translation, and RNA stability. Unbalanced m6A regulation will cause defects in adipogenesis, spermatogenesis, development, carcinogenesis, stem cell self-renewal and differentiation, and X-chromosome inactivation among others.
Figure 2
Figure 2. m6A RNA methylation regulates embryonic stem cell fate
(A) In naïve ESCs, depletion of Mettl3 results in a decrease of global m6A levels on developmental regulators which in turn promote ESC differentiation. (B) In naïve ESCs, ablation of Mettl3 results in a decrease of m6A at pluripotency RNAs. As a result, cells remain in a ‘hypernaïve’ pluripotent state and fail to differentiate. On the contrary, depletion of Zfp217 increases m6A deposition at pluripotency RNAs, promoting cell differentiation and/or cell death. In EpiSC, ablation of Mettl3 decreases m6A levels on developmental regulators, pushing cells towards differentiation and/or cell death. A and B reflect different models currently existing in the field.
See this image and copyright information in PMC

References

    1. Consortium EP. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489(7414):57–74. - PMC - PubMed
    1. Mohanty V, et al. Role of lncRNAs in health and disease-size and shape matter. Brief Funct Genomics. 2015;14(2):115–29. - PubMed
    1. Aguilo F, Di Cecilia S, Walsh MJ. Long Non-coding RNA ANRIL and Polycomb in Human Cancers and Cardiovascular Disease. Curr Top Microbiol Immunol. 2016;394:29–39. - PMC - PubMed
    1. Li S, Mason CE. The pivotal regulatory landscape of RNA modifications. Annu Rev Genomics Hum Genet. 2014;15:127–50. - PubMed
    1. Moore MJ. From birth to death: the complex lives of eukaryotic mRNAs. Science. 2005;309(5740):1514–8. - PubMed

MeSH terms

LinkOut - more resources