Trypanosoma cruzi eIF4E3- and eIF4E4-containing complexes bind different mRNAs and may sequester inactive mRNAs...

Area of Science:

• Molecular Biology
• Parasitology
• Gene Regulation

Background:

• Trypanosomes possess multiple paralogues of translation initiation factors like eIF4F and poly(A)-binding proteins (PABPs), unlike metazoans.
• These factors assemble into distinct complexes, each associated with specific messenger RNAs (mRNAs) and performing unique functions.

Purpose of the Study:

• To investigate the function and regulation of the two eIF4F complexes (eIF4E3 and eIF4E4) in the parasite *Trypanosoma cruzi*.
• To identify associated proteins and mRNAs under conditions of exponential growth and nutritional stress, which induces differentiation.

Main Methods:

• Analysis of protein and mRNA associations with eIF4E3 and eIF4E4 complexes.
• Comparison of complex composition and mRNA binding under growth and stress conditions.

Main Results:

• Two distinct eIF4F complexes (eIF4E3 and eIF4E4) were identified, each binding to different sets of mRNAs.
• Under nutritional stress, eIF4G and PABP remain associated with eIF4E, but ribosome attachment is reduced, indicating impaired translation initiation.
• eIF4E3-associated mRNAs primarily encode anabolic metabolism proteins, while eIF4E4 associates with ribosomal protein mRNAs.
• Despite lower translational efficiency under stress, both complexes bind to a greater number of mRNAs compared to non-stressed conditions.

Conclusions:

• *Trypanosoma cruzi* employs two co-existing eIF4F complexes that bind distinct mRNA populations.
• During stress-induced differentiation, these complexes exit translation but remain associated with their target mRNAs, suggesting a regulatory role beyond active translation.