Polyadenylate polymerases from normal and cancer cells and their potential role in messenger RNA processing: a review.
Two structurally and immunologically distinct species of nuclear polyadenylate [poly(A)] polymerases have been characterized. One of these enzymes is relatively absent in normal tissues but is predominant in primary and transplanted tumors and transformed cell lines. The presence of the tumor type enzyme in fetal liver, but not in regenerating liver, suggests that it is an oncofetal protein. Antibodies against the tumor-type poly(A) polymerases are present in the sera of rats bearing tumors and in some cancer patients. These antibodies are also found in the sera of rats fed hepatocarcinogen even before preneoplastic nodules were visible, which suggests that elicitation of these antibodies is an early event in neoplastic transformation. Autoantibodies against both liver-type and tumor-type poly(A) polymerase are also present in some rheumatic autoimmune sera. Polyclonal antibodies against purified enzyme from a rat hepatoma, which exhibit a single band upon immunoblot analysis, were used in cell-free extracts to study the role of poly(A) polymerase in the 3'-end processing of pre-mRNA. These studies showed that the antibodies blocked both endonucleolytic cleavage and poly(A) addition at the cleavage site and complex formation between factors in the extract and pre-mRNA. Independent studies in other laboratories have demonstrated that both the cleavage and poly(A) polymerase activities require the same component for their function. These observations suggest that both cleavage and polyadenylation reactions are tightly coupled in a functional complex.
Jacob
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Department of Pharmacology, Pennsylvania State University, College of Medicine, Hershey 17033.
Terns
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Maguire
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D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D000912:Antibodies, Neoplasm / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001483:Base Sequence; D055598:Chemical Phenomena; D002621:Chemistry; D008114:Liver Neoplasms, Experimental / Q000276:immunology; D008970:Molecular Weight; D009713:Nucleotidyltransferases / Q000502:physiology*; D009928:Organ Specificity; D011062:Polynucleotide Adenylyltransferase / Q000032:analysis / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D012216:Rheumatic Diseases / Q000276:immunology; D014158:Transcription, Genetic
D000974:Antibodies, Antinuclear; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D001323:Autoantibodies; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C031192:oncofetal antigens; D009713:Nucleotidyltransferases; D011062:Polynucleotide Adenylyltransferase