Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119994 Moscow, Russia.
Biochemistry (Mosc). 2013 Feb;78(2):157-65. doi: 10.1134/S0006297913020041.
We have earlier shown that the 5'-untranslated region (5' UTR) of the mRNA coding for activation factor of apoptotic peptidase 1 (Apaf-1) can direct translation in vivo by strictly 5' end-dependent way even in the absence of m(7)G-cap. Dependence of translational efficiency on the cap availability for this mRNA turned out to be relatively low. In this study we demonstrate that this surprising phenomenon is determined the 5'-proximal part (domains I and II) of highly structured Apaf-1 5' UTR. Remarkably, domain II by itself was able to reduce dependence of the mRNA on the cap on its transferring to a short 5' UTR derived from a standard vector. We suggest that the low cap-dependence inherent to some cellular mRNAs may have an important physiological significance under those stress conditions when the function of cap-binding factor eIF4E is impaired.
我们之前已经表明,凋亡蛋白酶激活因子 1(Apaf-1)mRNA 的 5'-非翻译区(5'UTR)可以通过严格的 5'端依赖方式指导体内翻译,即使在没有 m(7)G-帽的情况下也是如此。对于这种 mRNA,翻译效率对 cap 可用性的依赖性相对较低。在这项研究中,我们证明了这种令人惊讶的现象是由高度结构化的 Apaf-1 5'UTR 的 5'-近端部分(结构域 I 和 II)决定的。值得注意的是,单独的结构域 II 能够降低 mRNA 对其转移到来自标准载体的短 5'UTR 时对帽的依赖性。我们认为,在那些应激条件下,当帽结合因子 eIF4E 的功能受损时,某些细胞 mRNA 固有的低帽依赖性可能具有重要的生理意义。