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The biosynthesis and functional roles of methylated nucleosides in eukaryotic mRNA

  • Chapter
  • First Online:
Fine-Tuning of RNA Functions by Modification and Editing

Part of the book series: Topics in Current Genetics ((TCG,volume 12))

Abstract

Modified nucleosides are present in mRNA of all eukaryotes, albeit at much lower levels than in other RNA moieties such as rRNA, tRNA, and snRNA. Modification by methylation occurs on the terminal guanosine of the cap (N7-methylguanosine), and the first two encoded nucleosides (2’-O-methylnuculeosides) in most higher eukaryotes. Additional modifications of cap nucleosides occur in special cases where the cap is derived by transsplicing in nematodes and kinetoplastids. Modification by methylation also occurs at internal adenosine residues in many species (N6-methyladenosine). Modification by deamination occurs at specific adenosine residues (forming inosine) and cytidine residues (forming uridine) in very specific cases leading to post-transcriptional editing. Numerous studies have shown the importance of the cap N7-methylguanosine in translation, splicing, transport, and mRNA stability. The role of the 2’-O-methylnucleosides is not as well understood, but there is evidence that these modifications play some role in translation efficiency. The role of internal N6-methyladenosine residues is least known, and is the focus of this review. The formation of N6-methyladenosine is catalyzed by a complex enzyme containing a subunit (MT-A70) that co-localizes with nuclear speckles and appears to be widely expressed in all higher eukaryotes. Loss of this enzyme leads to a sporulation defect in yeast and to apoptosis in mammalian cells, although the exact mechanism by which the effects occur remains obscure.

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  1. Division of Hematology/Oncology, Department of Medicine and Center for RNA Molecular Biology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA

    Joseph A. Bokar

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  1. Joseph A. Bokar
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Correspondence to Joseph A. Bokar .

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Henri Grosjean

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Bokar, J.A. The biosynthesis and functional roles of methylated nucleosides in eukaryotic mRNA. In: Grosjean, H. (eds) Fine-Tuning of RNA Functions by Modification and Editing. Topics in Current Genetics, vol 12. Springer, Berlin, Heidelberg. https://doi.org/10.1007/b106365

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