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Identification of factors required for m$^{6}$A mRNA methylation in $\textit{Arabidopsis}$ reveals a role for the conserved E3 ubiquitin ligase HAKAI.

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Růžička, K 
Zhang, M 
Campilho, A 
Bodi, Z 
Kashif, M 


$\textit{N}6−adenosinemethylationm^{6}AofmRNAisanessentialprocessinmosteukaryotes,butitsroleandthestatusoffactorsaccompanyingthismodificationarestillpoorlyunderstood.Usingcombinedmethodsofgenetics,proteomicsandRNAbiochemistry,weidentifiedacoresetofmRNAm^{6}$A writer proteins in Arabidopsis thaliana. The components required for m6A in Arabidopsis included MTA, MTB, FIP37, VIRILIZER and the E3 ubiquitin ligase HAKAI. Downregulation of these proteins led to reduced relative m6A levels and shared pleiotropic phenotypes, which included aberrant vascular formation in the root, indicating that correct m6A methylation plays a role in developmental decisions during pattern formation. The conservation of these proteins amongst eukaryotes and the demonstration of a role in writing m6A for the E3 ubiquitin ligase HAKAI is likely to be of considerable relevance beyond the plant sciences.



Arabidopsis, HAKAI, N6-adenosine methylation (m6A), VIRILIZER, mRNA methylation, protoxylem

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New Phytologist

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Biotechnology and Biological Sciences Research Council (BB/N013158/1)
European Research Council (323052)
Supported by the Czech Science Foundation (P501/12/0934), European Social Fund (CZ.1.07/2.3.00/20.0189), the Ministry of Education, Youth and Sports of the Czech Republic (the National Program for Sustainability, NPUII-LQ1601 the NCLG Research Infrastructure, LM2015091, and the Czech-Biomaging, LM2015062) to K.R., M.S. and J.H. RNA methylation work in R.G.F.'s lab was supported by the Biotechnology and Biological Sciences Research Council (grant nos. BB/K013637/1 and BB/M008606/1). Y.H.'s laboratory was funded by the Gatsby Foundation (GAT3395/PR3); the National Science Foundation Biotechnology and Biological Sciences Research Council grant (BB/N013158/1); University of Helsinki (award 799992091), the European Research Council Advanced Investigator Grant SYMDEV (no. 323052); the Finnish Funding Agency for Technology and Innovation (Tekes); and the Academy of Finland Centre of Excellence program (award 63053034).