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N6-methyladenosine in poly(A) tails stabilize VSG transcripts.

Idálio J Viegas1, Juan Pereira de Macedo1, Lúcia Serra1

  • 1Instituto de Medicina Molecular-João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.

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|March 31, 2022
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Summary
This summary is machine-generated.

N6-methyladenosine (m6A) RNA modification regulates gene expression in Trypanosoma brucei, specifically within the poly(A) tail of variant surface glycoprotein transcripts, impacting mRNA stability.

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Area of Science:

  • Molecular Biology
  • Parasitology
  • RNA Biology

Background:

  • Gene expression in Trypanosoma brucei is primarily regulated post-transcriptionally due to its polycistronic transcription.
  • N6-methyladenosine (m6A) has been identified in Trypanosoma brucei, but its functional role is not understood.

Purpose of the Study:

  • To investigate the function of m6A RNA modification in Trypanosoma brucei.
  • To identify transcripts and regulatory elements associated with m6A modification.

Main Methods:

  • RNA immunoprecipitation to identify m6A-enriched transcripts.
  • Computational analysis to identify sequence motifs associated with m6A.
  • Genetic manipulation to assess the role of identified motifs in m6A regulation.

Main Results:

  • m6A modification is enriched in 342 transcripts, including those encoding variant surface glycoproteins (VSGs).
  • Approximately 50% of m6A is found in the poly(A) tail of VSG transcripts, removed before degradation.
  • A 16-mer motif in the 3' untranslated region of VSG genes is essential for m6A inclusion in the poly(A) tail.

Conclusions:

  • This study identifies m6A modification within the poly(A) tail of eukaryotic mRNA, a novel mechanism for post-transcriptional gene regulation.
  • The 16-mer motif acts as a cis-acting element controlling m6A incorporation and subsequent mRNA stability in Trypanosoma brucei.