mRNA localization by a 145-nucleotide region of the c-fos 3′-untranslated region -: Links to translation but not stability
mRNA localization by a 145-nucleotide region of the c-fos 3′-untranslated region -: Links to translation but not stability
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DOI：
10.1074/jbc.m001141200
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发表时间：
2001-04-27
影响因子：
4.8
通讯作者：
Hesketh, J
中科院分区：
文献类型：
--
作者：
Dalgleish, G;Veyrune, JL;Hesketh, J
通过原位杂交和细胞分级分离技术研究了 c-fos mRNA 3'-非翻译区中定位信号的存在。用嵌合基因构建体转染细胞，其中β-珠蛋白编码区用作报告基因并与其自身的3'-非翻译区、c-fos 3'-非翻译区或含有不同缺失的c-fos 3'-非翻译区连接。用来自c-fos的内源性β-珠蛋白3'-非翻译区替换内源性β-珠蛋白3'-非翻译区导致转录物的重新分布，使得它们在细胞骨架结合的多核糖体中被回收，并且位于核周细胞质中。富含AU的不稳定区域的删除并不影响转录物定位，但是去除3'-非翻译区的独特的145-核苷酸区域消除了它。去铁胺阻止转录本翻译导致转录本定位显着丧失，与 mRNA 不稳定性无关。数据显示，c-fos mRNA 的 3'-非翻译区（如 c-myc）包含定位信号，该信号将 mRNA 靶向核周细胞骨架。我们认为这对于确保这些关键调节蛋白的有效核输入非常重要。 fos 3'-非翻译区的 mRNA 定位与 mRNA 不稳定性无关，两者由不同的调控元件决定。
The presence of a localization signal in the 3'-untranslated region of c-fos mRNA was investigated by in situ hybridization and cell fractionation techniques. Cells were transfected with chimeric gene constructs in which the beta -globin coding region was used as a reporter and linked to either its own 3'-untranslated region, the c-fos 3'-untranslated region, or the c-fos 3'-untranslated region containing different deletions. Replacement of the endogenous beta -globin 3'-untranslated region by that from c-fos caused a redistribution of the transcripts so that they were recovered in cytoskeletal-bound polysomes and seen localized in the perinuclear cytoplasm, Deletion of the AU-rich instability region did not affect transcript localization, but removal of a distinct 145-nucleotide region of the 3'-untranslated region abolished it. The prevention of transcript translation by desferrioxamine led to a marked loss of transcript localization, independent of mRNA instability. The data show that the 3'-untranslated region of c-fos mRNA, as c-myc, contains a localization signal, which targets the mRNA to the perinuclear cytoskeleton. We propose that this is important to ensure efficient nuclear import of these key regulatory proteins. mRNA localization by the fos 3'-untranslated region is independent of mRNA instability, and the two are determined by different regulatory elements.