AU-rich elements (AREs) in 3 -untranslated regions of mRNAs confer instability. They target mRNAs for rapid deadenylation and degradation and may enhance decapping. The p38 MAPK pathway stabilizes many otherwise unstable ARE-containing mRNAs encoding proteins involved in inflammation; however, the mRNA decay step(s) regulated by the signaling pathway are unknown. To investigate whether it regulates deadenylation or the decay of the mRNA body, we used a tetracycline-regulated -globin mRNA reporter system to transcribe pulses of mRNA of uniform length. We measured on Northern gels the migration of reporter mRNAs isolated from cells transfected only with reporter plasmid or co-transfected with an active mutant of MAPK kinase-6, and treated either with or without the p38 MAPK inhibitor SB 203580. Differences in migration were shown by RNase H mapping with oligo(dT) to be due to poly(A) shortening. Insertion of an ARE into the -globin reporter mRNA promoted rapid deadenylation and decay of hypo-adenylated reporter mRNA. p38 MAPK activation inhibited the deadenylation of reporter mRNAs containing either the cyclooxygenase-2 or tumor necrosis factor AREs. The regulation of deadenylation by p38 MAPK was found to be specific because deadenylation of the -globin reporter mRNA either lacking an ARE or containing the c-Myc 3 -untranslated region (which is not p38 MAPK-responsive) was unaffected by p38 MAPK. It was concluded that the p38 MAPK pathway predominantly regulates deadenylation, rather than decay of the mRNA body, and this provides an explanation for why p38 MAPK regulates mRNA stability in some situations and translation in others.
A high proportion of dogs suffer from respiratory disease when they are placed in kennels for vacation or re-homing. The role of Mycoplasma cynos as an initiating agent in canine infectious respiratory disease was investigated by examining the serological response of dogs to this organism at the time of entry into a large re-homing kennel. Forty-two paired serum samples from dogs (21-day interval) were examined for antibody to M. cynos using Western blotting. The development of antibody in the serum was related to clinical disease recorded over the same period. Sixty seven per cent of the dogs showed a two-fold or greater rise in antibody to M. cynos during the first 3 weeks in the kennel. Reactivity with a 45kDa antigen was dominant. Of those showing a positive serological reaction, 80% had recorded clinical respiratory disease while 20% remained healthy. The findings of this study show that an antibody response to M. cynos is common in dogs entering the re-homing kennel and is positively related to the development of clinical respiratory disease.
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