Laird-Offringa I A, Elfferich P, van der Eb A J
Laboratory for Molecular Carcinogenesis, Sylvius Laboratories, University of Leiden, The Netherlands.
Nucleic Acids Res. 1991 May 11;19(9):2387-94. doi: 10.1093/nar/19.9.2387.
The c-myc proto-oncogene encodes a highly unstable mRNA. Stabilized, truncated myc transcripts have been found in several human and murine tumors of hematopoietic origin. Recently, two tumors expressing 3' truncated c-myc mRNAs that were five times more stable than normal myc transcripts, were described. We have tried to determine the cause of the increased stability of the 3' truncated myc transcripts by studying the half-life of mutated c-myc mRNAs. The c-myc 3' untranslated region has been shown to contain sequences that confer mRNA instability. Possible candidates for such sequences are two (A + U)-rich regions in the 3' end of the c-myc RNA that resemble RNA destabilizing elements present in the c-fos and GMCSF mRNAs. We show that deletions in the (A + U)-rich regions do not stabilize c-myc messengers, and that hybrid mRNAs containing SV40 sequences at their 3' ends and terminating at an SV40 polyadenylation signal decay as quickly as normal c-myc transcripts. Our results indicate that neither the loss of (A + U)-rich sequences nor the mere addition of non-myc sequences to the 3' end of the mRNA lead to stabilization. We also show that rapid degradation of c-myc mRNA does not require complete translation of the coding sequences.
c-myc原癌基因编码一种高度不稳定的mRNA。在几种造血系统来源的人类和鼠类肿瘤中发现了稳定的、截短的myc转录本。最近，描述了两种表达3'截短的c-myc mRNA的肿瘤，其稳定性比正常myc转录本高五倍。我们试图通过研究突变的c-myc mRNA的半衰期来确定3'截短的myc转录本稳定性增加的原因。c-myc 3'非翻译区已被证明含有赋予mRNA不稳定性的序列。这类序列的可能候选者是c-myc RNA 3'端的两个富含（A+U）的区域，它们类似于c-fos和GMCSF mRNA中存在的RNA不稳定元件。我们发现，富含（A+U）区域的缺失并不会使c-myc信使RNA稳定，并且3'端含有SV40序列并在SV40聚腺苷酸化信号处终止的杂交mRNA与正常c-myc转录本一样迅速降解。我们的结果表明，富含（A+U）序列的缺失以及仅仅在mRNA 3'端添加非myc序列都不会导致稳定。我们还表明，c-myc mRNA的快速降解不需要编码序列的完全翻译。
