7-Methylguanosine-dependent inhibition of globin mRNA translation by methylglyoxal.
Studies on the inhibition of translation by methylglyoxal of capped and chemically decapped globin mRNAs in the rabbit reciculocyte system strongly suggest that it is cap-dependent. Concentrations of methylglyoxal (0.2 mM), which effected substantial inhibition (80%) of capped mRNA, were only slightly inhibitory (10%) to the decapped species. In addition, the inhibition was K+-dependent with maximal inhibition occurring at the K+ optimum for translation of the capped species, suggesting cap recognition is required for the effect. Results with endogenous mRNA further substantiate that initiation and not elongation is the site of action. These results are consistent with an inhibition due to a newly discovered, rapid reaction of methylglyoxal with the 7-methylguanosine of the cap structure.
D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005914:Globins / Q000096:biosynthesis*; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D011188:Potassium / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects*; D011765:Pyruvaldehyde / Q000494:pharmacology*; D012315:RNA Caps / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism
D000447:Aldehydes; D012315:RNA Caps; D012333:RNA, Messenger; D006151:Guanosine; C016578:7-methylguanosine; D011765:Pyruvaldehyde; D005914:Globins; D011188:Potassium