N⁶-Methyladenosine on Key Messenger RNAs Governs Reproductive Development and Metabolic Adaptation in Human Blood...

Area of Science:

• Molecular Biology
• Parasitology
• Epigenetics

Background:

• Schistosomiasis affects over 250 million people globally.
• Parasite survival and egg production are key to schistosomiasis pathology.
• The role of N⁶-methyladenosine (m⁶A) RNA modification in parasitic helminths is unknown.

Purpose of the Study:

• To characterize the m⁶A landscape in *Schistosoma japonicum*.
• To investigate the functional roles of m⁶A modification in parasite development and physiology.
• To explore the m⁶A pathway as a potential therapeutic target.

Main Methods:

• High-resolution transcriptome-wide m⁶A mapping in male and female parasites.
• Functional analysis of the m⁶A writer complex (METTL3/14).
• RNA sequencing and methylated RNA immunoprecipitation sequencing after METTL3 knockdown.

Main Results:

• Distinct sex-specific m⁶A patterns were identified.
• m⁶A is essential for female reproduction and egg-laying.
• m⁶A is vital for male parasite integrity, metabolism, and motility.
• Key m⁶A-modified transcripts, including glutamine synthetase, were identified.

Conclusions:

• This study provides the first functional evidence of m⁶A epitranscriptomic regulation in a parasitic helminth.
• m⁶A acts as a master regulator of reproductive and somatic development in *S. japonicum*.
• The m⁶A pathway represents a promising target for novel schistosomiasis control strategies.