DIFFERENTIAL MESSENGER-RNA STABILITIES AFFECT MESSENGER-RNA LEVELS IN MUTANT MOUSE MYELOMA CELLS

A series of mouse myeloma cell lines producing mutant gamma-2b immunoglobulin 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 gamma-2b-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 gamma-2b-CH2 and CH3 domain, causing premature termination of translation, had more deleterious effects on Ig heavy chain mRNA abundance and half-life (mutant I17). Substitution of the deleted portions of the gamma-2b mRNA with gamma-2a sequences by subclass switching in the cells (mutants K23 and K25) resulted in increased heavy chain abundance and half-life relative to the parent I17. 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 gamma-2b locus equally when compared with an internal beta-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.