title: Novel metabolism of several beta zero-thalassemic beta-globin mRNAs in the erythroid tissues of transgenic mice.
abstract: Mice that are transgenic for human beta zero-thalassemic beta-globin alleles were generated in order to study how beta zero-thalassemic mutations affect beta-globin RNA metabolism in erythroid tissues. Three thalassemic alleles were studied, each of which harbors either a frameshift or a nonsense mutation. These mutations result in the premature termination of beta-globin mRNA translation and an abnormally low level of beta-globin mRNA in the peripheral blood of thalassemic patients. Comparative studies of mice that express any of the beta zero-thalassemic transgenes with mice that express a normal human beta-globin transgene demonstrated that all three thalassemic mRNAs are metabolized in erythroid tissues abnormally. RNA blotting and S1 nuclease transcript mapping revealed for each thalassemic transgene that (i) the full-length mRNA is abnormally short-lived and (ii) in addition to full-length mRNA, three more stable yet smaller RNAs are present. These smaller RNAs are polyadenylated and lack the mRNA 5' end.
authors.affiliation: Department of Human Genetics, Roswell Park Memorial Institute, Buffalo, NY 14263.
authors.forename: S
authors.initials: S
authors.lastname: Lim
authors.forename: J J
authors.initials: JJ
authors.lastname: Mullins
authors.forename: C M
authors.initials: CM
authors.lastname: Chen
authors.forename: K W
authors.initials: KW
authors.lastname: Gross
authors.forename: L E
authors.initials: LE
authors.lastname: Maquat
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005091:Exons; D005914:Globins / Q000235:genetics*; D006801:Humans; D007558:Italy; D007585:Jews / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010957:Plasmids; D011061:Poly A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013728:Terminator Regions, Genetic; D013789:Thalassemia / Q000235:genetics*; D014162:Transfection; D014421:Turkey
chemical_list: D012333:RNA, Messenger; D011061:Poly A; D005914:Globins