Modulation of messenger RNA metabolism in experimental methyl mercury neurotoxicity. 1987

D A Kuznetsov, and V Richter

We have investigated the effects of methyl mercury of mRNA metabolism in mouse brain cells in vivo. It was demonstrated that methyl mercury substantially reduces the rate of synthesis of ATP and poly(A)-segments of mRNAs. The molecular sizes of poly(A)-segments isolated from hnRNA and polysomal mRNA of the experimental animal brain are smaller than the dimensions of the same segments from the cellular RNA of intact mice. A fall in the mRNA polyadenylation rate seen under methyl mercury directly correlates with reduced metabolic stability (t 1/2) of the respective poly(A)+mRNA. The mean time of nuclear-cytoplasmic transport of these mRNAs (t0 is substantially increased under methyl mercury. At the same time, methyl mercury has no effect on the metabolism of brain polysomal poly(A)-mRNA. Direct addition of methyl mercury to an in vitro system containing excess ATP failed to affect the activity of poly(A) polymerase isolated from the brain of intact mice. The poison-induced alterations in the poly(A)+mRNA metabolism bring about a considerable reduction of the poly(A)+-fraction's share in the total polysomal mRNA and dramatic fall in the intracellular polysomes concentration. All the alterations in the examined metabolic parameters well correlate both with a reduced ATP content in the brain tissue and decreased rate of total protein synthesis in brain cells. Proceeding from these results as well as data from the literature, we developed a hypothetical model of a general molecular mechanism whereby methyl mercury inhibits protein synthesis in the brain.

UI MeSH Term Description Entries
D008297 Male Males
D008767 Methylmercury Compounds Organic compounds in which mercury is attached to a methyl group. Methyl Mercury Compounds,Compounds, Methyl Mercury,Compounds, Methylmercury,Mercury Compounds, Methyl
D008808 Mice, Inbred CBA An inbred strain of mouse that is widely used in BIOMEDICAL RESEARCH. Mice, CBA,Mouse, CBA,Mouse, Inbred CBA,CBA Mice,CBA Mice, Inbred,CBA Mouse,CBA Mouse, Inbred,Inbred CBA Mice,Inbred CBA Mouse
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D011061 Poly A A group of adenine ribonucleotides in which the phosphate residues of each adenine ribonucleotide act as bridges in forming diester linkages between the ribose moieties. Adenine Polynucleotides,Polyadenylic Acids,Poly(rA),Polynucleotides, Adenine
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D001923 Brain Chemistry Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states. Chemistry, Brain,Brain Chemistries,Chemistries, Brain
D000255 Adenosine Triphosphate An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

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