Human-like eukaryotic translation initiation factor 3 from Neurospora crassa.

Human-like eukaryotic translation initiation factor 3 from Neurospora crassa.
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DOI:
10.1371/journal.pone.0078715
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Cate JH
Cate JH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Smith MD;Gu Y;Querol-Audí J;Vogan JM;Nitido A;Cate JH

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真核翻译起始因子3(eIF3)是翻译起始的关键调节因子,但其在体内的组装和分子功能尚不清楚。在这里,我们表明,eIF3从粗糙脉孢菌的结构和组成类似于人eIF3。n. crassa eIF3形成稳定的12-亚基复合物,该复合物与第13亚基eIF3j在遗传和生物化学上连接,eIF3j在人类中调节mRNA起始密码子选择。基于N. crassa遗传分析表明,eIF3中的大多数亚基是必需的。可以删除的亚基(e、h、k和l)映射到eIF3复合物的右侧,表明它们可能协调调节eIF3功能。与该模型一致,亚基eIF3k和eIF3l作为一对被并入eIF3复合物中,并且它们的插入取决于亚基eIF3h的存在,eIF3h是脊椎动物发育的关键调节因子。与其他eIF3复合物的比较表明,eIF3围绕eIF3a和eIF3c二聚体组装,这可以解释人类eIF3水平的协调调节。总之,这些结果表明,粗糙脉孢菌eIF3提供了一个易于处理的系统,用于探测在活细胞的背景下类人eIF3的结构和功能。
Eukaryotic translation initiation factor 3 (eIF3) is a key regulator of translation initiation, but its in vivo assembly and molecular functions remain unclear. Here we show that eIF3 from Neurospora crassa is structurally and compositionally similar to human eIF3. N. crassa eIF3 forms a stable 12-subunit complex linked genetically and biochemically to the 13th subunit, eIF3j, which in humans modulates mRNA start codon selection. Based on N. crassa genetic analysis, most subunits in eIF3 are essential. Subunits that can be deleted (e, h, k and l) map to the right side of the eIF3 complex, suggesting that they may coordinately regulate eIF3 function. Consistent with this model, subunits eIF3k and eIF3l are incorporated into the eIF3 complex as a pair, and their insertion depends on the presence of subunit eIF3h, a key regulator of vertebrate development. Comparisons to other eIF3 complexes suggest that eIF3 assembles around an eIF3a and eIF3c dimer, which may explain the coordinated regulation of human eIF3 levels. Taken together, these results show that Neurospora crassa eIF3 provides a tractable system for probing the structure and function of human-like eIF3 in the context of living cells.
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