Plasmodium falciparum translational machinery condones polyadenosine repeats

Area of Science:

• Molecular Biology
• Parasitology
• Genetics

Background:

• * Plasmodium falciparum, the causative agent of malaria, possesses an extremely AT-rich genome (81%).
• * A significant portion (60%) of its mRNAs contain long polyadenosine (polyA) runs within coding regions.
• * PolyA runs in other organisms typically cause ribosome stalling and frameshifting, activating mRNA surveillance and reducing protein synthesis.

Purpose of the Study:

• * To investigate the translation efficiency and accuracy of long polyA runs in P. falciparum.
• * To determine if polyA runs trigger mRNA surveillance pathways like No Go Decay (NGD) in this parasite.
• * To compare the parasite's response to polyA runs with that of human cells and other AT-rich organisms.

Main Methods:

• * Translation of endogenous genes and reporter constructs containing long polyA runs in P. falciparum cells.
• * Assessment of ribosome stalling using reporter sequences.
• * Analysis of frameshifting and mRNA surveillance pathway activation (NGD).
• * Comparative studies in human cells and Tetrahymena thermophila.

Main Results:

• * Long polyA runs are efficiently and accurately translated in P. falciparum.
• * PolyA runs do not induce ribosome stalling or frameshifting in the parasite.
• * No Go Decay (NGD) pathway is not activated by polyA runs in P. falciparum.
• * Plasmodium cells exhibit a non-functional NGD pathway, contrasting with human cells and T. thermophila.

Conclusions:

• * P. falciparum exhibits a unique mechanism for handling long polyA runs, allowing efficient translation.
• * The parasite has evolved to bypass the detrimental effects of polyA runs observed in other organisms.
• * The lack of a fully functional No Go Decay (NGD) pathway is a key adaptation in Plasmodium for managing its AT-rich transcriptome.