Lozano F, Maertzdorf B, Pannell R, Milstein C
Medical Research Council Centre, Laboratory of Molecular Biology, Cambridge, UK.
EMBO J. 1994 Oct 3;13(19):4617-22. doi: 10.1002/j.1460-2075.1994.tb06783.x.
We have previously reported down-regulation of mRNA expression of some of the kappa light chain transgenes in a hybridoma derived from a secondary immune response. Of the five heavily mutated transgene copies present in that hybridoma, three included premature stop codons and were 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 evidence that the reduction in mRNA abundance was attributable to an increased rate of cytoplasmic mRNA decay, the amount of cytoplasmic mRNA correlated with the accumulation of unspliced transcripts in the nucleus. Similar results were obtained with a chimeric immunoglobulin gene containing a premature chain termination codon in the variable gene segment. We suggest that inhibition of splicing induced by in-frame premature stop codons is an important mechanism for down-regulation of undesirable immunoglobulin transcripts.
我们之前报道过，在源自二次免疫应答的杂交瘤中，一些κ轻链转基因的mRNA表达下调。在该杂交瘤中存在的五个高度突变的转基因拷贝中，三个包含过早的终止密码子，并且在mRNA水平上表达水平较低。在这里我们表明，无义突变是mRNA水平低的原因。虽然我们没有发现证据表明mRNA丰度的降低归因于细胞质mRNA降解速率的增加，但细胞质mRNA的量与细胞核中未剪接转录本的积累相关。在可变基因片段中含有过早链终止密码子的嵌合免疫球蛋白基因也获得了类似的结果。我们认为，框内过早终止密码子诱导的剪接抑制是下调不良免疫球蛋白转录本的重要机制。
