Differential m6A methylomes between two major life stages allows potential regulations in Trypanosoma brucei

Luogen Liu1, Shinuan Zeng2, Hongtao Jiang3

  • 1Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080, China; Clinic Research Center, The Second Affiliated Hospital, University of South China, Hengyang, 421001, China.

Insights

N6-methyladenosine (m6A) modification is abundant in Trypanosoma brucei, impacting gene expression across its life stages. This study reveals m6A

Area of Science:

  • * Molecular Biology
  • * Epigenetics
  • * Parasitology

Background:

  • * N6-methyladenosine (m6A) is a prevalent mRNA modification in eukaryotes, regulating gene expression.
  • * Trypanosoma brucei (T. brucei) relies on post-transcriptional regulation, but internal mRNA modifications were previously unreported.
  • * Understanding m6A in T. brucei could reveal novel regulatory mechanisms in this parasite.

Purpose of the Study:

  • * To investigate the presence and distribution of m6A modification in T. brucei.
  • * To characterize the m6A methylome across different life stages of T. brucei.
  • * To identify potential m6A reader proteins in T. brucei.

Main Methods:

  • * Transcriptome-wide m6A methylome profiling in procyclic and bloodstream forms of T. brucei.
  • * Bioinformatic analysis to identify m6A consensus motifs and associated genes.
  • * RNA pulldown assays to identify m6A-binding proteins.

Main Results:

  • * m6A modification is abundant in T. brucei, with 355 peaks in procyclic and 95 in bloodstream forms.
  • * A conserved CAU motif was identified for m6A sites in both life stages.
  • * m6A-containing transcripts showed higher abundance in procyclic forms, longer half-lives, and enrichment in cell morphology/movement pathways; TRRM2 was identified as a potential m6A reader.

Conclusions:

  • * This study presents the first transcriptome-wide m6A methylome in T. brucei.
  • * m6A modification plays a significant role in regulating gene expression and mRNA stability in T. brucei.
  • * The identification of TRRM2 suggests a novel m6A-dependent post-transcriptional regulatory pathway in this parasite.

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