Trypanosoma cruzi eIF4E3- and eIF4E4-containing complexes bind different mRNAs and may sequester inactive mRNAs during nutritional stress

Abstract

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