Shen-Ong G L
Laboratory of Genetics, National Cancer Institute, Bethesda, MD 20892.
EMBO J. 1987 Dec 20;6(13):4035-9. doi: 10.1002/j.1460-2075.1987.tb02748.x.
Activation of the c-myb gene by viral transduction or proviral insertional mutagenesis that is likely to result in the production of structurally altered myb proteins has been shown to be predominantly associated with myelomonocytic tumors. An alternative splicing event in which a portion of the intron bounded by the vE6 and vE7 exons with v-myb homology is included as an additional 363-nucleotide coding exon has recently been identified in a mouse tumor that carries a provirus-activated myb gene. This alternative splicing was hypothesized to be a tumor-specific aberrant form of 3'-myb RNA processing as a consequence of the disruption of upstream 5'-sequences by proviral insertion. However, RNA blot analyses and RNase mapping studies presented here show that a significant portion (approximately 10%) of all myb transcripts examined, whether in normal or in clonal tumor cells, contains the additional exon. Hence the alternative splicing is a hitherto unrecognized common normal event that potentially increases the diversity of the myb proteins expressed in normal tissues including thymus and spleen, as well as in tumor cells with either normal or 5'-rearranged myb alleles. The lack of change in the ratio of the two spliced products expressed from either the normal or the 5'-rearranged myb further indicates that the insertion of the unique 121 amino acids in the larger myb transcripts is not a consequence of tumor-specific activation of the mouse myb oncogene.
病毒转导或前病毒插入诱变激活c-myb基因，可能导致结构改变的myb蛋白产生，这主要与骨髓单核细胞肿瘤相关。最近在一个携带前病毒激活的myb基因的小鼠肿瘤中，发现了一种可变剪接事件，其中与v-myb具有同源性的、由vE6和vE7外显子界定的部分内含子，被作为一个额外的363个核苷酸的编码外显子包含在内。这种可变剪接被假定为是由于前病毒插入破坏上游5'序列，从而导致的3'-myb RNA加工的肿瘤特异性异常形式。然而，本文给出的RNA印迹分析和RNase图谱研究表明，在所有检测的myb转录本中，无论在正常细胞还是克隆肿瘤细胞中，都有很大一部分（约10%）包含这个额外的外显子。因此，这种可变剪接是一种迄今未被认识到的常见正常事件，它可能增加在包括胸腺和脾脏在内的正常组织以及具有正常或5'-重排myb等位基因的肿瘤细胞中表达的myb蛋白的多样性。正常或5'-重排myb表达的两种剪接产物的比例没有变化，这进一步表明，较大的myb转录本中独特的121个氨基酸的插入，不是小鼠myb癌基因肿瘤特异性激活的结果。
