Structure, Activity and Function of the Dual Protein Lysine and Protein N-Terminal Methyltransferase METTL13

Overview

Journal Life (Basel)

Specialty Biology

Date 2021 Nov 27

PMID 34832997

Citations 5

Authors

Magnus E Jakobsson

Affiliations

Soon will be listed here.

Abstract

METTL13 (also known as eEF1A-KNMT and FEAT) is a dual methyltransferase reported to target the N-terminus and Lys55 in the eukaryotic translation elongation factor 1 alpha (eEF1A). METTL13-mediated methylation of eEF1A has functional consequences related to translation dynamics and include altered rate of global protein synthesis and translation of specific codons. Aberrant regulation of METTL13 has been linked to several types of cancer but the precise mechanisms are not yet fully understood. In this article, the current literature related to the structure, activity, and function of METTL13 is systematically reviewed and put into context. The links between METTL13 and diseases, mainly different types of cancer, are also summarized. Finally, key challenges and opportunities for METTL13 research are pinpointed in a prospective outlook.

Citing Articles

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METTL Family in Healthy and Disease.

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References

Arnesen T, Van Damme P, Polevoda B, Helsens K, Evjenth R, Colaert N . Proteomics analyses reveal the evolutionary conservation and divergence of N-terminal acetyltransferases from yeast and humans. Proc Natl Acad Sci U S A. 2009; 106(20):8157-62. PMC: 2688859. DOI: 10.1073/pnas.0901931106. View

Petkowski J, Bonsignore L, Tooley J, Wilkey D, Merchant M, Macara I . NRMT2 is an N-terminal monomethylase that primes for its homologue NRMT1. Biochem J. 2013; 456(3):453-62. PMC: 4086624. DOI: 10.1042/BJ20131163. View

Dong C, Dong G, Li L, Zhu L, Tempel W, Liu Y . An asparagine/glycine switch governs product specificity of human N-terminal methyltransferase NTMT2. Commun Biol. 2018; 1:183. PMC: 6214909. DOI: 10.1038/s42003-018-0196-2. View

Schubert H, Blumenthal R, Cheng X . Many paths to methyltransfer: a chronicle of convergence. Trends Biochem Sci. 2003; 28(6):329-35. PMC: 2758044. DOI: 10.1016/S0968-0004(03)00090-2. View

Wu H, Min J, Ikeguchi Y, Zeng H, Dong A, Loppnau P . Structure and mechanism of spermidine synthases. Biochemistry. 2007; 46(28):8331-9. DOI: 10.1021/bi602498k. View

Schwanhausser B, Gossen M, Dittmar G, Selbach M . Global analysis of cellular protein translation by pulsed SILAC. Proteomics. 2008; 9(1):205-9. DOI: 10.1002/pmic.200800275. View

Petrossian T, Clarke S . Uncovering the human methyltransferasome. Mol Cell Proteomics. 2010; 10(1):M110.000976. PMC: 3013446. DOI: 10.1074/mcp.M110.000976. View

Marcos E, Mazur A, Cardot P, Rayssiguier Y . Quantitative determination of apolipoprotein B in bovine serum by radial immunodiffusion. Comp Biochem Physiol B. 1989; 94(1):171-3. DOI: 10.1016/0305-0491(89)90029-1. View

Diaz K, Meng Y, Huang R . Past, present, and perspectives of protein N-terminal methylation. Curr Opin Chem Biol. 2021; 63:115-122. PMC: 8384643. DOI: 10.1016/j.cbpa.2021.02.017. View

10.

Li Y, Kobayashi K, Mona M, Satomi C, Okano S, Inoue H . Immunogenic FEAT protein circulates in the bloodstream of cancer patients. J Transl Med. 2016; 14(1):275. PMC: 5034574. DOI: 10.1186/s12967-016-1034-2. View

11.

Jakobsson M, Moen A, Falnes P . Correspondence: On the enzymology and significance of HSPA1 lysine methylation. Nat Commun. 2016; 7:11464. PMC: 4915027. DOI: 10.1038/ncomms11464. View

12.

Kapell S, Jakobsson M . Large-scale identification of protein histidine methylation in human cells. NAR Genom Bioinform. 2021; 3(2):lqab045. PMC: 8140740. DOI: 10.1093/nargab/lqab045. View

13.

Ong S, Mittler G, Mann M . Identifying and quantifying in vivo methylation sites by heavy methyl SILAC. Nat Methods. 2005; 1(2):119-26. DOI: 10.1038/nmeth715. View

14.

Pohl C, Dikic I . Cellular quality control by the ubiquitin-proteasome system and autophagy. Science. 2019; 366(6467):818-822. DOI: 10.1126/science.aax3769. View

15.

Dong C, Mao Y, Tempel W, Qin S, Li L, Loppnau P . Structural basis for substrate recognition by the human N-terminal methyltransferase 1. Genes Dev. 2015; 29(22):2343-8. PMC: 4691889. DOI: 10.1101/gad.270611.115. View

16.

Chen P, Sobreira T, Hall M, Hazbun T . Discovering the N-Terminal Methylome by Repurposing of Proteomic Datasets. J Proteome Res. 2021; 20(9):4231-4247. DOI: 10.1021/acs.jproteome.1c00009. View

17.

Bekker-Jensen D, Kelstrup C, Batth T, Larsen S, Haldrup C, Bramsen J . An Optimized Shotgun Strategy for the Rapid Generation of Comprehensive Human Proteomes. Cell Syst. 2017; 4(6):587-599.e4. PMC: 5493283. DOI: 10.1016/j.cels.2017.05.009. View

18.

Cloutier P, Lavallee-Adam M, Faubert D, Blanchette M, Coulombe B . A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity. PLoS Genet. 2013; 9(1):e1003210. PMC: 3547847. DOI: 10.1371/journal.pgen.1003210. View

19.

Liu S, Hausmann S, Carlson S, Fuentes M, Francis J, Pillai R . METTL13 Methylation of eEF1A Increases Translational Output to Promote Tumorigenesis. Cell. 2019; 176(3):491-504.e21. PMC: 6499081. DOI: 10.1016/j.cell.2018.11.038. View

20.

Black J, Van Rechem C, Whetstine J . Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell. 2012; 48(4):491-507. PMC: 3861058. DOI: 10.1016/j.molcel.2012.11.006. View