Fresno M, Vázquez D
Eur J Biochem. 1980 Jan;103(1):125-32. doi: 10.1111/j.1432-1033.1980.tb04296.x.
The cap analogues 7-methylguanosine 5'-phosphate [m7G(5')p], 7-methylguanosine 5'-triphosphate [m7G(5')ppp] and 2'-O-methylguanosine 5'-triphosphate [Gm(5')ppp] inhibit the translation of capped globin mRNA and encephalomyocarditis (EMC) RNA (a naturally uncapped mRNA) in a reticulocyte cell-free system. This inhibition occurs at the level of protein synthesis initiation and is of a competitive type since it can be overcome by increasing the mRNA concentration. However, the translation of globin mRNA is more sensitive to the inhibitory effects of the cap analogues m7G(5')p and m7G(5')ppp than translation of EMC RNA. The same spectra of specific inhibition is also observed with some other initiation inhibitors such as aurintricarboxylic acid, which inhibits mRNA binding, but not with pactamycin which does not affect mRNA interaction. A model is presented suggesting that this preferential inhibition by cap analogues could be explained mainly by the different affinities of globin mRNA and EMC RNA for the initiation complexes between 40-S subunits and Met-tRNAf. Moreover Gm(5')ppp cannot be considered simply as a cap analogue since it also affects some step prior to mRNA binding.
帽类似物7-甲基鸟苷5'-磷酸[m7G(5')p]、7-甲基鸟苷5'-三磷酸[m7G(5')ppp]和2'-O-甲基鸟苷5'-三磷酸[Gm(5')ppp]在网织红细胞无细胞体系中可抑制加帽珠蛋白mRNA和脑心肌炎病毒(EMC)RNA(一种天然无帽的mRNA)的翻译。这种抑制发生在蛋白质合成起始水平，且属于竞争性抑制，因为增加mRNA浓度可克服这种抑制。然而，珠蛋白mRNA的翻译比EMC RNA的翻译对帽类似物m7G(5')p和m7G(5')ppp的抑制作用更敏感。用其他一些起始抑制剂如金精三羧酸(抑制mRNA结合)也观察到相同的特异性抑制谱，但对不影响mRNA相互作用的 pactamycin则未观察到。本文提出了一个模型，表明帽类似物的这种优先抑制作用主要可由珠蛋白mRNA和EMC RNA对40-S亚基与甲硫氨酰-tRNAf之间起始复合物的不同亲和力来解释。此外，Gm(5')ppp不能简单地被视为帽类似物，因为它还影响mRNA结合之前的某些步骤。
