3'-end mRNA processing within apicomplexan parasites, a patchwork of classic, and unexpected players

Area of Science:

• Molecular Biology
• RNA Biology
• Parasitology

Background:

• mRNA 3'-end processing is crucial for gene expression, involving cleavage and polyadenylation specificity factors (CPSF).
• CPSF recognizes mRNA sequences, mediating cleavage and polyadenylation, essential for transcription termination.
• Understanding CPSF machinery in diverse eukaryotes, including Apicomplexa, is vital due to its conserved yet divergent roles.

Purpose of the Study:

• To review the convergence and divergence of CPSF function in apicomplexan parasites.
• To explore the significance of the N6-methyladenosine (m6A) reader integrated into apicomplexan CPSF.
• To investigate the potential of small molecule inhibitors targeting CPSF in these organisms.

Main Methods:

• Review of recent structural and biochemical studies on CPSF.
• Analysis of conserved and divergent features of CPSF in apicomplexans.
• Exploration of m6A metabolism and its link to 3'-end processing.

Main Results:

• CPSF is conserved in Apicomplexa but uniquely integrates an m6A reader, a feature from the plant kingdom.
• This integration connects m6A metabolism directly to mRNA 3'-end processing and transcription termination.
• Structural and biochemical data illuminate CPSF mechanisms in yeast and metazoans, providing context for apicomplexan divergence.

Conclusions:

• Apicomplexan CPSF represents an ancient machinery with novel adaptations, particularly the m6A reader.
• The m6A integration highlights a conserved link between RNA modification and gene expression regulation.
• Targeting CPSF with small molecules presents a potential therapeutic strategy against apicomplexan parasites.