Does the Pb(2+)-catalyzed depolymerization of RNA occur in vivo.
In order to determine if Pb2+ depolymerizes RNA, reticulocytes were transfused into rabbits that had been dosed with lead acetate and also into untreated controls. The messenger RNA from these reticulocytes was the examined to determine if in vivo exposure to the Pb2+ had impaired the integrity of the mRNA. The total amount of mRNA did not vary between controls and Pb(2+)-treated rabbits. However, when the ability of the mRNA to program protein synthesis in cell-free hemolysates was tested, a marked loss in biological activity of the mRNA from the Pb(2+)-treated rabbits was observed. That the loss in biological activity was due to the depolymerization of the mRNA in vivo was shown by an increase in the number of free 5' hydroxyl groups in the poly (A+) RNA from the Pb(2+)-treated rabbits. The ratio of polyribosomes to monoribosomes was also decreased. In vitro experiments on the effects of Pb2+ on globin mRNA were also performed and showed that at micromolar Pb2+ concentrations the mRNA was attacked in the vicinity of the 5' end with little damage to the rest of the molecule. These data show that Pb2+ catalyzes cleavage of phosphodiester bonds resulting in loss of template activity of mRNA in vivo as well as in vitro.
Aethranis
C A
CA
College of Veterinary Medicine, University of Tennessee, Knoxville 37901-1071, USA.
Farkas
W
W
D000818:Animals; D001798:Blood Proteins / Q000096:biosynthesis; D002384:Catalysis; D017707:Erythrocyte Transfusion; D066298:In Vitro Techniques; D007854:Lead / Q000097:blood / Q000633:toxicity*; D009942:Organometallic Compounds / Q000633:toxicity; D011108:Polymers / Q000737:chemistry / Q000378:metabolism; D011132:Polyribosomes / Q000187:drug effects; D012333:RNA, Messenger / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D011817:Rabbits; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation
D001798:Blood Proteins; D009942:Organometallic Compounds; D011108:Polymers; D012333:RNA, Messenger; D007854:Lead; C008261:lead acetate