Structural basis for eukaryotic mRNA modification

Abstract

All messenger RNAs in eukaryotes are modified co-transcriptionally and post-transcriptionally. They are all capped at the 5'-end and polyadenylated at the 3'-end. However, many mRNAs are also found to be chemically modified internally for regulation of mRNA processing, translation, stability, and to recode the message. This review will briefly summarize the structural basis for formation of the two most common modifications found at internal sites in mRNAs; methylation and deamination. The structures of the enzymes that catalyze these modifications show structural similarity to other family members within each modifying enzyme class. RNA methyltransferases, including METTL3/METTL14 responsible for N-methyladensosine (mA) formation, share a common structural core and utilize S-adenosyl methionine as a methyl donor. RNA deaminases, including adenosine deaminases acting on RNA (ADARs), also share a common structural core and similar signature sequence motif with conserved residues used for binding zinc and catalyzing the deamination reaction. In spite of recent reports of high resolution structures for members of these two RNA-modifying enzyme families, a great deal remains to be uncovered for a complete understanding of the structural basis for mRNA modification. Of particular interest is the definition of factors that control modification site specificity.

Context-aware synthetic biology by controller design: Engineering the mammalian cell

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Chemical tagging for sensitive determination of uridine modifications in RNA

“…11 The technical breakthroughs led to the discovery of a series of modications in eukaryotic mRNA, including N 6methyladenosine (m 6 A), N1-methyladenosine (m 1 A), N 6 ,2 0 -Odimethyladenosine (m 6 Am), 5-methylcytidine (m 5 C), N3-methylcytidine (m 3 C), N7-methylguanosine (m 7 G), 2 0 -O-methylation, inosine (I), and pseudouridine (J). [11][12][13] Very recently, N 4 -acetylcytidine was newly discovered to be present in mRNA of mammals. 14 These studies demonstrated that the modications play versatile roles in mRNA processing and eventually affect the epitranscriptomic state of cells.…”

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