Modified Nucleosides in Rna — Their Formation and Function

Both ribosomal RNA (rRNA) and transfer RNA (tRNA) are fundamental to protein synthesis. It is therefore not surprising that the synthesis of these RNA species constitutes a major biosynthetic pathway in the cell. Both rRNA and tRNA contain modified nucleosides, which are derivatives of the ordinary nucleosides adenosine (A), guanosine (G), cytidine (C) and uridine (U) (Figure 1). It was earlier believed that this was a unique feature of all stable RNAs, but it has now been established that the stable 5S RNA does not contain any modified nucleosides. ¹ Although mRNA from Escherichia coli does not contain methylated nucleosides, ² the mRNA from eukaryotic organisms does (see chapters by Moss and Flint, this volume). Except for 5S RNA all other rRNA and tRNA species so far investigated contain modified nucleosides but to varying degrees. Both rRNA as well as tRNA are initially made as larger transcripts than their mature products. Several endo- and exonucleases operate during the stepwise maturation of RNA (reviewed in this book by other authors). However, during maturation several of the four ordinary nucleosides, A, G, C, and U are enzymatically modified in a specific manner. Such modifications occur concomitantly to processing of the primary transcription products and thus are an integrated part of the maturation process. Therefore, all modification reactions except one (see below) occur at the polynucleotide level, i.e., after the polymerization by the DNA-dependent-RNA polymerase. Modified nucleosides are derivatives of the four ordinary nucleosides, and Figure 1 shows some structures of modified nucleosides (e.g., l-methylguanosinetm’G) contains a methyl group in position 1 of guanosine, etc.). A more complete catalog of structures of modified nucleosides has recently been published. ³ This review concentrates on recent results of the dynamic process of modification, i.e., its genetics, its regulation of formation, and its functional aspects. Earlier results and some other aspects of modification which are not discussed here are excellently dealt with elsewhere. ^{4 - 16}