THE 3'-UNTRANSLATED REGIONS OF C-MOS AND CYCLIN MESSENGER-RNAS STIMULATE TRANSLATION BY REGULATING CYTOPLASMIC POLYADENYLATION
THE 3'-UNTRANSLATED REGIONS OF C-MOS AND CYCLIN MESSENGER-RNAS STIMULATE TRANSLATION BY REGULATING CYTOPLASMIC POLYADENYLATION
复制标题
DOI：
10.1101/gad.8.8.926
复制
发表时间：
1994-04-15
影响因子：
10.5
通讯作者：
WICKENS, M
中科院分区：
文献类型：
--
作者：
SHEETS, MD;FOX, CA;WICKENS, M
在许多动物发育的早期，在转录开始之前，蛋白质合成模式的任何变化都可归因于卵中mRNA的翻译活性或稳定性的变化。因此，翻译控制是至关重要的各种发展的决定，包括轴的形成在果蝇和秀丽隐杆线虫的性别决定。以前的工作表明，增加poly（A）的长度可以激活翻译，而删除poly（A）可以防止it. In这份报告中，我们专注于控制c-mos和细胞周期蛋白A1，B1和B2 mRNA在减数分裂成熟和受精后的青蛙卵。我们发现，从这些mRNA中添加和去除poly（A）是广泛调节的：每个mRNA接收或丢失poly（A）的时间，以及它获得或丢失的腺苷的数量，有很大的不同。每个mRNA的3 '-非翻译区（UTR）中的信号足以重建poly（A）添加的时间和定量控制：嵌合mRNA（其中一个内切酶编码区连接到细胞周期蛋白A1、细胞周期蛋白B1或c-mos mRNA的3' UTR）与内源性mRNA一样，在相同的时间接受相同长度的poly（A）。此外，每个3' UTR还调节嵌合mRNA的翻译，决定成熟期间荧光素酶报告基因的翻译何时以及多少被刺激。荧光素酶活性的刺激幅度从5倍变化到100倍，这取决于3' UTR。每个3' UTR的翻译刺激需要poly（A）延长，因为它被阻止该过程的突变所阻止。这些结果表明，细胞周期蛋白和c-mos mRNA的3'UTR不仅控制mRNA在成熟过程中是否打开，还控制激活何时发生以及激活程度。c-mos mRNA的翻译控制可以通过调节poly（A）长度来实现，这在成熟的激活和裂解分裂的开始中可能是至关重要的。我们的研究结果，以及其他人的研究结果，表明，即使是相当复杂的模式，翻译激活在早期胚胎可以通过差异控制一个共同的机制。
Early in the development of many animals, before transcription begins, any change in the pattern of protein synthesis is attributable to a change in the translational activity or stability of an mRNA in the egg. As a result, translational control is critical for a variety of developmental decisions, including axis formation in Drosophila and sex determination in Caenorhabditis elegans. Previous work demonstrated that increases in poly(A) length can activate translation, whereas removal of poly(A) can prevent it. In this report we focus on the control of c-mos and cyclin A1, B1, and B2 mRNAs during meiotic maturation and after fertilization of frog eggs. We show that addition and removal of poly(A) from these mRNAs is extensively regulated: The time at which each mRNA receives or loses poly(A), as well as the number of adenosines it gains or loses, differ substantially. Signals in the 3'-untranslated region (UTR) of each mRNA are sufficient to reconstitute both the temporal and quantitative control of poly(A) addition: Chimeric mRNAs in which a luciferase-coding region is joined to the 3' UTRs of cyclin A1, cyclin B1, or c-mos mRNA, receive poly(A) of the same length and at the same time as do the endogenous mRNAs. Moreover, each 3' UTR also regulates translation of the chimeric mRNAs, determining when and how much translation of the luciferase reporter is stimulated during maturation. The magnitude of stimulation in luciferase activity varies from 5- to 100-fold, depending on the 3' UTR. Translational stimulation by each 3' UTR requires poly(A) lengthening, as it is prevented by mutations that prevent that process. These results suggest that the 3' UTRs of cyclin and c-mos mRNAs control not only whether or not an mRNA is turned on during maturation, but when that activation occurs and to what extent. Translational control of c-mos mRNA, which may be achieved through regulation of poly(A) length, may be critical in the activation of maturation, and in the onset of cleavage divisions. Our findings, as well as those of others, suggest that even quite complex patterns of translational activation in the early embryo can be attained through the differential control of a common mechanism.