An axonemal intron splicing program sustains Plasmodium male development.

Area of Science:

• Malaria parasite biology
• Molecular parasitology
• Post-transcriptional gene regulation

Background:

• Male gametogenesis in Plasmodium is essential for mosquito transmission.
• RNA-binding proteins (RBPs) regulate gene expression post-transcriptionally.
• The specific role of RBPs in male Plasmodium development is not fully understood.

Purpose of the Study:

• To identify male-specific RBPs in Plasmodium.
• To investigate the function of a novel RBP, RBPm1, in male gametogenesis.
• To elucidate the mechanism of RBPm1 in regulating axoneme assembly.

Main Methods:

• Genome-wide screening for gender-specific RBPs.
• Generation and analysis of RBPm1-deficient Plasmodium parasites.
• Interaction studies with the spliceosome complex.
• Splicing assays using reporter and endogenous genes.
• Analysis of axonemal gene expression and protein production.

Main Results:

• Identified a novel male-specific RBP, RBPm1, essential for Plasmodium male gametogenesis.
• RBPm1 deficiency leads to failed axoneme assembly and impaired mosquito transmission.
• RBPm1 interacts with the spliceosome and regulates splicing initiation of 26 axonemal genes.
• RBPm1 deficiency causes intron retention and loss of axonemal proteins.
• Intron deletion partially rescues axonemal defects.

Conclusions:

• RBPm1 is a critical splicing activator for axonemal genes.
• An axonemal intron splicing program regulated by RBPm1 is essential for male gametogenesis.
• RBPm1 plays a vital role in the post-transcriptional regulation required for malaria parasite transmission.