LOW CYTOPLASMIC MESSENGER-RNA LEVELS OF IMMUNOGLOBULIN-KAPPA LIGHT-CHAIN GENES CONTAINING NONSENSE CODONS CORRELATE WITH INEFFICIENT SPLICING

We have previously reported down-regulation of mRNA expression of some of the kappa light chain transgenes in a hybridoma derived from a sec ondary immune response. Of the five heavily mutated transgene copies p resent in that hybridoma, three included premature stop codons and wer e poorly represented at the mRNA level. Here we show that the nonsense mutations are the cause of the low mRNA levels. While we found no evi dence that the reduction in mRNA abundance was attributable to an incr eased rate of cytoplasmic mRNA decay, the amount of cytoplasmic mRNA c orrelated with the accumulation of unspliced transcripts in the nucleu s. Similar results were obtained with a chimeric immunoglobulin gene c ontaining a premature chain termination codon in the variable gene seg ment. We suggest that inhibition of splicing induced by in-frame prema ture stop codons is an important mechanism for down-regulation of unde sirable immunoglobulin transcripts.