RNA base damage and repair.
Elaborate repair pathways counteract the deleterious effects of DNA damage by mechanisms that are understood in reasonable detail. In contrast, repair of damaged RNA has not been widely explored. This may be because aberrant RNAs are generally assumed to be degraded rather than repaired. The reason for this view is well founded, since conserved surveillance mechanisms that degrade abnormal RNAs are thoroughly documented. Numerous proteins and protein-RNA complexes are involved in the metabolism of different RNA species, assuring correct transcription, splicing, posttranscriptional modifications, transport, translation and timely degradation of the molecule. However, like DNA, RNA is under constant attack of various environmental and endogenous agents that damage the molecule, such as alkylating agents, radiation and free radicals. Importantly, many DNA damaging drugs used in cancer therapy also modify RNA, presumably causing delayed or faulty translation. This may result in generation of inactive proteins, dominant negative proteins or toxic protein aggregates. Several lines of evidence indicate RNA repair as a possible cellular defence mechanism to cope with RNA damage. Thus, there are convincing examples of tRNA repair by elongation of truncated forms, and repair of cleaved tRNA by T4 phage proteins. In addition, in vitro repair of aberrant tRNA methylation by a methyl transferase has been reported. Finally, recent reports on repair of chemically methylated RNA by AlkB and a human homologue (hABH3) in vitro and in vivo strengthen the idea of RNA base repair as a cellular defence mechanism.
Feyzi
Emadoldin
E
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway.
Sundheim
Ottar
O
Westbye
Marianne Pedersen
MP
Aas
Per Arne
PA
Vågbø
Cathrine B
CB
Otterlei
Marit
M
Slupphaug
Geir
G
Krokan
Hans E
HE
D000071500:AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase; D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics; D049308:Dioxygenases / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics; D006801:Humans; D008745:Methylation; D006899:Mixed Function Oxygenases / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics*
D029968:Escherichia coli Proteins; D012313:RNA; D006899:Mixed Function Oxygenases; D049308:Dioxygenases; C486439:ALKBH3 protein, human; D000071500:AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase; C466427:AlkB protein, E coli; D045643:DNA Repair Enzymes