Gabiatti Bernardo Papini, Freire Eden Ribeiro, Ferreira da Costa Jimena, Ferrarini Mariana Galvão, Reichert Assunção de Matos Tatiana, Preti Henrique, Munhoz da Rocha Isadora, Guimarães Beatriz Gomes, Kramer Susanne, Zanchin Nilson Ivo Tonin, Holetz Fabíola Barbieri
Carlos Chagas Institute, Oswaldo Cruz Foundation, FIOCRUZ, R. Prof. Algacyr Munhoz Mader 3775, 81350-010, Curitiba-PR, Brazil.
Biocenter, University of Würzburg, Am Hubland 97074, Würzburg, Germany.
Nucleic Acids Res. 2025 Jan 11;53(2). doi: 10.1093/nar/gkae1181.
Many eIF4F and poly(A)-binding protein (PABP) paralogues are found in trypanosomes: six eIF4E, five eIF4G, one eIF4A and two PABPs. They are expressed simultaneously and assemble into different complexes, contrasting the situation in metazoans that use distinct complexes in different cell types/developmental stages. Each eIF4F complex has its own proteins, messenger RNAs (mRNAs) and, consequently, a distinct function. We set out to study the function and regulation of the two eIF4F complexes of the parasite Trypanosoma cruzi and identified the associated proteins and mRNAs of eIF4E3 and eIF4E4 in cells in exponential growth and in nutritional stress, an inducer of differentiation to an infective stage. Upon stress, eIF4G and PABP remain associated with the eIF4E, but the associations with other 43S pre-initiation factors decrease, indicating ribosome attachment is impaired. Most eIF4E3-associated mRNAs encode for proteins involved in anabolic metabolism, while eIF4E4 associate with mRNAs encoding ribosomal proteins as in Trypanosoma brucei. Interestingly, for both eIF4E3/4, more mRNAs were associated in stressed cells than in non-stressed cells, even though these have lower translational efficiencies in stress. In summary, trypanosomes have two co-existing eIF4F complexes associating to different mRNAs, but not stress/differentiation-associated mRNAs. Under stress, both complexes exit translation but remain bound to their mRNA targets.
在锥虫中发现了许多真核起始因子4F（eIF4F）和聚腺苷酸结合蛋白（PABP）的旁系同源物：六个eIF4E、五个eIF4G、一个eIF4A和两个PABP。它们同时表达并组装成不同的复合物，这与后生动物在不同细胞类型/发育阶段使用不同复合物的情况形成对比。每个eIF4F复合物都有其自身的蛋白质、信使核糖核酸（mRNA），因此具有独特的功能。我们着手研究寄生虫克氏锥虫的两种eIF4F复合物的功能和调控，并鉴定了处于指数生长期的细胞以及在营养应激（一种诱导分化为感染阶段的因素）条件下eIF4E3和eIF4E4的相关蛋白质和mRNA。在应激状态下，eIF4G和PABP仍与eIF4E结合，但与其他43S起始前因子的结合减少，这表明核糖体附着受损。大多数与eIF4E3相关的mRNA编码参与合成代谢的蛋白质，而与eIF4E4相关的mRNA则如布氏锥虫那样与编码核糖体蛋白的mRNA结合。有趣的是，对于eIF4E3/4两者而言，应激细胞中相关的mRNA比非应激细胞中的更多，尽管这些mRNA在应激状态下的翻译效率较低。总之，锥虫有两种共存的eIF4F复合物，它们与不同的mRNA结合，但不与应激/分化相关的mRNA结合。在应激状态下，两种复合物都停止翻译，但仍与它们的mRNA靶标结合。
