Translational control by adenovirus: lack of virus-associated RNAI during adenovirus infection results in phosphorylation of initiation factor eIF-2 and inhibition of protein synthesis.
Translational control by adenovirus: lack of virus-associated RNAI during adenovirus infection results in phosphorylation of initiation factor eIF-2 and inhibition of protein synthesis.
复制标题
腺病毒的翻译控制：腺病毒感染期间缺乏病毒相关的 RNAI 会导致起始因子 eIF-2 磷酸化并抑制蛋白质合成。
DOI：
10.1073/pnas.82.7.1959
复制
发表时间：
1985
影响因子：
11.1
通讯作者：
Mathews,MB
中科院分区：
文献类型：
--
作者：
Siekierka,J;Mariano,TM;Reichel,PA;Mathews,MB
5型腺病毒的dl331突变体不能产生病毒相关的RNAi，并且感染该突变体的细胞在感染后期不能有效地合成蛋白质。翻译缺陷发生在多肽链起始水平，从感染d1331的细胞制备的无细胞提取物显示出体内观察到的缺陷。在这些无细胞提取物中加入真核生物起始因子2(eIF-2)或鸟嘌呤核苷酸交换因子(Gef)可以恢复翻译活性，而gef在这方面发挥更有效的作用。这些结果表明，感染dl331突变体的细胞在全球环境基金催化的鸟核苷酸交换水平上形成了翻译阻断，并且这种阻断很可能是通过磷酸化eIF-2的α亚基来建立的。在目前的研究中，我们发现在感染dl331突变体的细胞中，内源性HeLa细胞的gef活性显着降低。此外，与野生型血清2型腺病毒感染的细胞相比，d1331感染的细胞含有更高的eIF-2α激酶活性。这些结果表明，在腺病毒感染HeLa细胞的过程中，VA RNAi具有抑制eIF-2α激酶活性的作用。
The dl331 mutant of adenovirus serotype 5 fails to produce virus-associated (VA) RNAI, and cells infected with this mutant do not synthesize proteins efficiently at late times in infection. The translational defect occurs at the level of polypeptide chain initiation, and cell-free extracts prepared from dl331-infected cells exhibit the defect observed in vivo. Addition of either eukaryotic initiation factor 2 (eIF-2) or guanine nucleotide exchange factor (GEF) to these cell-free extracts restores translational activity, with GEF functioning more efficiently in this regard. These results suggest that cells infected with the dl331 mutant develop a translational block at the level of GEF-catalyzed guanine nucleotide exchange and that this block is most likely established through phosphorylation of the alpha subunit of eIF-2. In the present investigation we show that endogenous HeLa cell GEF activity is significantly reduced in cells infected with the dl331 mutant. Further, in contrast to cells infected with wild-type serotype 2 adenovirus, dl331-infected cells contain increased eIF-2 alpha kinase activity. These results indicate that VA RNAI plays a role in suppressing eIF-2 alpha kinase activity during adenovirus infection of HeLa cells.
基因表达调控中翻译和转录控制的相互作用
DOI：
--
发表时间：
1983
期刊：
影响因子：
--
作者：
J. Ninio
通讯作者：
J. Ninio