Hann S R
Department of Cell Biology, Vanderbilt University, School of Medicine, Nashville, TN 37232-2175.
Biochimie. 1994;76(9):880-6. doi: 10.1016/0300-9084(94)90190-2.
A small, yet growing, number of cellular eukaryotic mRNAs encoding important regulatory proteins, such as c-myc and other proto-oncogenes, initiate translation from a non-AUG codon, usually in addition to initiating at a downstream AUG. The efficiency of non-AUG initiation on these natural cellular mRNAs varies considerably and appears to be governed by several features, including the codon sequence, the context surrounding the codon and the secondary structure of the transcript. In addition to factors which control the overall efficiency of c-myc non-AUG initiation, the relative efficiency of the upstream non-AUG initiation compared with the AUG initiation changes during the growth of cells. As lymphoid and fibroblast cells approach high densities in culture there is a sustained 5-10-fold induction in the synthesis of the non-AUG-initiated c-Myc 1 protein to levels comparable to or greater than the AUG-initiated c-Myc 2 protein. This increased efficiency of c-myc non-AUG initiation, due to methionine depletion of the growth medium, suggests that the scanning preinitiation complex can be regulated to enhance the recognition of a suboptimal non-AUG codon. The significance of non-AUG initiation for the growth-regulatory genes is illustrated by the different localizations of the int-2, bFGF and hck non-AUG-initiated proteins, the disruption of the c-myc and lyl-1 non-AUG initiation in tumor-derived cell lines, and the distinct biological function of the non-AUG-initiated forms of bFGF.
一小部分但数量在不断增加的编码重要调节蛋白（如c-myc和其他原癌基因）的细胞真核mRNA，从非AUG密码子起始翻译，通常除了在下游AUG起始翻译外。这些天然细胞mRNA上非AUG起始的效率差异很大，似乎受几个特征的支配，包括密码子序列、密码子周围的上下文以及转录本的二级结构。除了控制c-myc非AUG起始总体效率的因素外，上游非AUG起始与AUG起始相比的相对效率在细胞生长过程中会发生变化。当淋巴细胞和成纤维细胞在培养中接近高密度时，非AUG起始的c-Myc 1蛋白的合成会持续诱导5至10倍，达到与AUG起始的c-Myc 2蛋白相当或更高的水平。由于生长培养基中蛋氨酸的消耗，c-myc非AUG起始效率的提高表明，扫描起始前复合物可以被调节以增强对次优非AUG密码子的识别。非AUG起始对生长调节基因的重要性体现在int-2、bFGF和hck非AUG起始蛋白的不同定位、肿瘤衍生细胞系中c-myc和lyl-1非AUG起始的破坏以及bFGF非AUG起始形式的独特生物学功能上。
