Enzymatic Modification and Editing of RNAs: a Guided Tour

Chemically modified deoxyribo- and ribo-nucleosides, derived from adenosine, guanosine, cytidine, thymidine or uridine, are found in all types of nucleic acid. To date, 26 modified (non-canonical) nucleosides have been identified in DNA and 107 in RNA. They are particularly abundant in non-coding RNAs, such as transfer RNAs and ribosomal RNAs, especially in metazoans. By increasing the structural diversity of nucleic acids, they play an important role in gene expression and the fine regulation of various RNA functions, notably gene translation. They also contribute to the thermal stability and protection of nucleic acids against nuclease action and viral aggression. In a cell, the number and diversity of enzymes required to selectively modify certain nucleosides of RNA or DNA, as well as to generate the same modification but at distinct sites of a nucleic acid, is very high. The problem is to understand: i) when and why these numerous enzymes emerged and evolved since life first appeared on earth; ii) where they are located in contemporary cells (free or associated with other cellular components) and how they function (mechanism and specificity).

We draw particular attention to the type and function of the modified nucleosides present in the anticodon of transfer RNAs. Some of these modified nucleosides (and their corresponding modifying enzymes) are very old, while others emerged later in the evolutionary process. Among the most important evolutionary constraints are the need for in-phase, highly-precise gene translation at the level of the ribosome-messenger RNA complex, the gradual introduction of the 20 + 2 canonical amino acids, and the gradual convergence towards an almost universal genetic code, enabling Combinatorics evolutionary synergies between different species in the three life domains.

For general or detailed information on the discovery, biochemical and physical properties of the nucleic acid (DNA or RNA) modifying and editing enzymes identified so far, the reader can refer to several chapters written (in English) by specialists in the following books:

Grosjean H. (ed), DNA and RNA modification Enzymes: Structure, Mechanism, Function and Evolution, Austin (Texas), Landes Bioscience, 2009(http://www.landesbioscience.com/curiechapter/4181/).
Grosjean H. (ed), Fine-Tuning of RNA Functions by Modification and Editing, Berlin-Heidelberg, Springer-Verlag, 2005(http://www.springerlink.com/content/?k=RNA+Modification+Editing).
Grosjean H. and Benne R.(eds.), Modification and Editing of RNA, Washington-DC, ASM Press, 1998.
Grosjean H., de Crécy-Lagard V. and Marck C., "Deciphering synonymous codons in the three domains of Life: Co-evolution with specific tRNA modification enzymes", FEBS Letters, a Special Issue on tRNA, 584, 2010, 252-264.