Cap-independent polysomal association of natural mRNAs encoding c-myc, BiP, and eIF4G conferred by internal ribosome entry sites
Cap-independent polysomal association of natural mRNAs encoding c-myc, BiP, and eIF4G conferred by internal ribosome entry sites
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DOI：
10.1017/s1355838298981080
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发表时间：
1998-12-01
期刊：
影响因子：
4.5
通讯作者：
Sarnow, P
中科院分区：
文献类型：
--
作者：
Johannes, G;Sarnow, P
已经在某些无帽病毒和加帽细胞mRNA分子的5'非编码区中鉴定出可以作为内部核糖体进入位点（IRES）的序列元件。然而，当IRES元件位于其天然加帽mRNA中时，其是否具有功能仍然是未知的。因此，在严重抑制帽依赖性翻译的条件下，即脊髓灰质炎病毒感染后，检测了几种含IRES的细胞mRNA的多核糖体缔合和翻译。研究发现，当大多数宿主细胞mRNA的帽依赖性翻译被阻断时，几种已知的含有IRES的mRNA，如BiP和c-myc，都与翻译装置相关，并在感染的细胞中翻译，这表明IRES元件在其天然mRNA中具有功能。令人好奇的是，编码真核起始因子4GI（eIF 4GI）和4GII（eIF 4GII）的mRNA，这两种在帽依赖性翻译起始中具有高度同一性和相似功能的蛋白质，都与感染细胞中的多核糖体相关。从cDNA表达文库中分离eIF 4GI mRNA的5 '端序列，并显示当置于双顺反子mRNA中时作为内部核糖体进入位点起作用。这些发现表明，eIF 4G蛋白可以在5'帽依赖性mRNA翻译被阻断时合成，支持eIF 4G蛋白在5'帽非依赖性和5'帽依赖性翻译起始机制中都需要的观点。
Sequence elements that can function as internal ribosome entry sites (IRES) have been identified in 5' noncoding regions of certain uncapped viral and capped cellular mRNA molecules. However, it has remained largely unknown whether IRES elements are functional when located in their natural capped mRNAs. Therefore, the polysomal association and translation of several IRES-containing cellular mRNAs was tested under conditions that severely inhibited cap-dependent translation, that is, after infection with poliovirus. It was found that several known IRES-containing mRNAs, such as BiP and c-myc, were both associated with the translation apparatus and translated in infected cells when cap-dependent translation of most host-cell mRNAs was blocked, indicating that the IRES elements were functional in their natural mRNAs. Curiously, the mRNAs that encode eukaryotic initiation factor 4GI (eIF4GI) and 4GII (eIF4GII), two proteins with high identity and similar functions in the initiation of cap-dependent, translation, were both associated with polysomes in infected cells. The 5'-end sequences of eIF4GI mRNA were isolated from a cDNA expression library and shown to function as an internal ribosome entry site when placed into a dicistronic mRNA. These findings suggest that eIF4G proteins can be synthesized at times when 5' cap-dependent mRNA translation is blocked, supporting the notion that eIF4G proteins are needed in both 5' cap-independent and 5' cap-dependent translational initiation mechanisms.