N6-methyladenosine Modulates Messenger RNA Translation Efficiency

By Xiao Wang, B. Zhao, I. A. Roundtree, Zhike Lu, Dali Han, Honghui Ma, X. Weng, Kai Chen, Hailing Shi, Chuan He. Cell, 2015

3,084 citations recorded by the source corpus.

SUMMARY N6-methyladenosine (m6A) is the most abundant internal modification in mammalian mRNA. This modification is reversible and non-stoichiometric and adds another layer to the dynamic control of mRNA metabolism. The stability of m6A-modified mRNA is regulated by an m6A reader protein, human YTHDF2, which recognizes m6A and reduces the stability of target transcripts. Looking at additional functional roles for the modification, we find that anotherm6A reader protein, human YTHDF1, actively promotes protein synthesis by interacting with translation machinery. In a unified mechanism of m6A-based regulation in the cytoplasm, YTHDF2-mediated degradation controls the lifetime of target transcripts, whereas YTHDF1-mediated translation promotion increases translation efficiency, ensuring effective protein production from dynamic transcripts that are marked by m6A. Therefore, the m6A modification in mRNA endows gene expression with fast responses and controllable protein production through these mechanisms.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/59f62645f626406375f637b2b5865c791ef57e0c

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Molecular Biology

1. Chuan He
2. Samie R. Jaffrey
3. S. Zaccara
4. Kate D. Meyer
5. Hailing Shi
6. Jiangbo W
7. Jianzhao Liu
8. Y. Yue

Citations in the corpus

• METTL3 promotes translation in human cancer cells (2016, methodology): “It was recently reported that YTHDF1 binds to the m6A sites and can enhance translation by interacting with eIF3 (Wang et al., 2015).”
• FMRP Modulates Neural Differentiation through m6A-Dependent mRNA Nuclear Export (2019, neutral): “…(m 6 A) is emerging as a critical mechanism regulating different aspects of RNA metabolism and function, including stability (Du et al., 2016; Ke et al., 2017; Wang et al., 2014), localization (Roundtree et al., 2017), and translation (Lin et al., 2016; Meyer et al., 2015; Wang et al., 2015).”
• METTL14 suppresses the metastatic potential of hepatocellular carcinoma by modulating N6‐methyladenosine‐dependent primary MicroRNA processing (2017, background): “Accumulating evidence demonstrates that variant m(6)A levels exert diverse biological functions in mammals, such as transcription splicing,((11)) nuclear RNA export,((12)) protein translation control,((13)) and cell fate determination.”
• Structural basis for cooperative function of Mettl3 and Mettl14 methyltransferases (2016, neutral): “Addition of m6A can alter mRNA stability, induce RNA conformational changes, modulate protein-RNA interactions, and even modify microRNA processing (Alarcón et al., 2015; Liu et al., 2015b; Wang et al., 2014a, 2015; Zhou et al., 2016).”
• m6A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer (2018, positive): “Because m 6 A methylation appeared to promote the expression of PHLPP2, we hypothesized that PHLPP2 transcripts are targets of YTHDF1, the m 6 A reader protein that promotes translation of m 6 A methylated transcripts 16 .”