Differential mRNA stabilities affect mRNA levels in mutant mouse myeloma cells
Tóm tắt
A series of mouse myeloma cell lines producing mutant γ2b immunoglobin heavy chains, which resemble heavy chain disease proteins, were analyzed for messenger RNA abundance as a function of mRNA alterations. A mutation effectively deleting the γ2b-CH1 domain of the mRNA had little or no effect on Ig heavy chain mRNA abundance on half-life (mutant 10.1). A mutation in the γ2b-CH2 and CH3 domain, causing premature termination of translation, had more deleterious effects on Ig heavy chain mRNA abundance and half-life (mutant 117). Substitution of the deleted portions of the γ2b mRNA with γ2a sequences by subclass switching in the cells (mutants K23 and K25) resulted in increased heavy chain abundance and half-life relative to the parent 117. In contrast, kappa light chain mRNA levels and half-lives remain constant among the mutants. The wild-type and mutant cell lines transcribed the Ig heavy chain γ2b locus equally when compared with an internal β-actin standard by transcription run on studies. Therefore, half-life of the Ig heavy chain mRNA seems to be the principal determinant in cytoplasmic mRNA abundance in this system.
Tài liệu tham khảo
Frangione, B., and Franklin, E.C. (1973).Semin. Hematol. 1053–64.
Franklin, E.C., and Frangione, B. (1975).Contemp. Top. Mol. Immunol. 489–126.
Seligmann, M., Michaesco, E., Preud'Homme, J.L., Danon, F., and Brouet, J.C. (1979).Immunol. Rev. 48145–167.
Guglielmi, P., Bakhshi, A., Cogne, M., Seligmann, M., and Korsmeyer, S.J. (1988).J. Immunol. 1411762–1768.
Cogne, M., Bakhshi, A., Korsmeyer, S.J., and Guglielmi, P. (1988).J. Immunol. 1411738–1744.
Eckhardt, L.A., and Birshtein, B.K. (1985).Mol. Cell. Biol. 5856–868.
Tilley, S.A., Eckhardt, L.A., Marcu, K.B., and Birshtein, B.K. (1983).Proc. Natl. Acad. Sci. U.S.A. 806967–6971.
Gilmore, G.C., Bard, J.A., and Birshtein, B.K. (1988).J. Immunol. 1411754–1761.
Ollo, R., Auffray, C., Morchamps, C., and Rougeon, F. (1981).Proc. Natl. Acad. Sci. U.S.A. 782442–2446.
Ollo, R., and Rougeon, F. (1983).Cell 32515–523.
Brandt, C.R., Morrison, S.L., Birshtein, B.K., and Milcarek, C. (1984).Mol. Cell. Biol. 41270–1277.
Kobrin, B., Glass, K., Morrison, S.L., and Milcarek, C. (1988).Mol. Immunol. 25181–187.
Morrison, S.L. (1979).J. Immunol. 123793–800.
Monk, R.J., Morrison, S.L., and Milcarek, C. (1981).Biochemistry 202330–2339.
Altenburger, W., Steinmetz, M., and Zachau, H.G. (1980).Nature 287603–607.
Darnell, J.E., Jr. (1982).Nature 297365–371.
Nevins, J.R. (1983).Annu. Rev. Biochem. 52441–466.
Kelly, D.E., and Perry, R.P. (1986).Nucleic Acids Res. 145431–5447.
Genovese, C., and Milcarek, C. (1990).Mol. Immunol. 27733–743.
Laskov, R., and Scharff, M.D. (1970).J. Exp. Med. 131515–541.
Mohit, B. (1971).Proc. Natl. Acad. Sci. U.S.A. 683045–3048.
Schwinghamer, M.W., and Shepherd, R.J. (1980).Anal. Biochem. 103426–434.
Thomas, P. (1980).Proc. Natl. Acad. Sci. U.S.A. 775201–5205.
Amasino, R.M. (1986).Anal. Biochem. 152304–307.
Church, G.M., and Gilbert, W. (1984).Proc. Natl. Acad. Sci. U.S.A. 811991–1995.
Maniatis, T., Jeffrey, A., and Kleid, D.G. (1975).Proc. Natl. Acad. Sci. U.S.A. 721184–1188.
Tucker, P.W., Marcu, K.B., Slightom, J.L., and Blattner, F.R. (1979).Science 2061299–1303.
Schibler, U., Marcu, K.B., and Perry, R.P. (1978).Cell 151495–1509.
Tucker, P.W., Marcu, K.B., Newell, N., Richards, J., and Blattner, F.R. (1979).Science 2061303–1306.
Minty, A.J., Alonso, S., Guenet, J.L., and Buckingham, M.E. (1983).J. Mol. Biol. 16777–101.
Milcarek, C., and Hall, B. (1985).Mol. Cell. Biol. 52514–2520.
Losson, R., and Lacroute, F. (1979).Proc. Natl. Acad. Sci. U.S.A. 765134–5137.
Maquat, L.E., Kinniburgh, A.J., Rachmilewitz, E.A., and Ross, J. (1981).Cell 27543–553.
Hargrove, J.L., and Schmidt, F.H. (1989).FASEB J. 32360–2370.
Baumann, B., Potash, M.J., and Kohler, G. (1985).EMBO J. 4351–359.
Daar, I.O., and Maquat, L.E. (1988).Mol. Cell. Biol. 8802–813.
Brawerman, G. (1987).Cell 485–6.
Jack, H.M., and Wabl, M. (1988).EMBO J. 71041–1046.
Mason, J.O., Williams, G.T., and Neuberger, M.S. (1988).Genes Dev. 21003–1011.