Can tRNAs act as antisense RNA? The case of mutA and dnaQ.
Many mutator genes have been characterized in E. coli, but the realization that mutA, the most recent mutator pathway described, encodes for a missense suppressor glycine tRNA caused a real surprise. The connection between expression of mutA and a 10 times increase in the spontaneous mutation rate is not readily explainable. The first attempt to describe the mechanism of action suggested a direct mistranslation of one subunit of polymerase III (PolIII) and the ideal candidate was the epsilon subunit carrying the 3'-->5' exonuclease activity. This subunit increases PolIII accuracy about 100 times. However, such direct mistranslation of epsilon was later ruled out when it became clear that all mutA cells express an error-prone form of PolIII. This result could not be reconciled with the very low level of mistranslation (1%) caused by mutA. But there is no need to invoke amino acid misincorporation in epsilon to destroy its activity. On the contrary, I suggest a new way to regulate epsilon amount, based on the reinterpretation of the mutA pathway through the new and puzzling observation that several tRNAs (including mutA which encodes for a glycine missense suppressor tRNA) are complementary to the 5' end of dnaQ mRNA. Accordingly, I propose that uncharged tRNAs can act as antisense RNAs, decreasing translation of dnaQ and possibly other genes. This could represent a new regulatory function for tRNAs and of course gives a direct and unrecognized link between starvation and mutation rate.
Dorazi
Robert
R
1 rue des Acacias, Jarny 54800, France. rdorazi@hotmail.com
D000818:Animals; D001426:Bacterial Proteins; D001430:Bacteriocins; D004258:DNA Polymerase III / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics*; D008957:Models, Genetic; D020125:Mutation, Missense; D010455:Peptides / Q000235:genetics*; D014176:Protein Biosynthesis; D016372:RNA, Antisense; D012343:RNA, Transfer / Q000235:genetics*
D001426:Bacterial Proteins; D001430:Bacteriocins; D029968:Escherichia coli Proteins; D010455:Peptides; D016372:RNA, Antisense; C110490:mutacin II prepeptide, bacteria; D012343:RNA, Transfer; D004258:DNA Polymerase III; C468316:dnaQ protein, E coli