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A role for Caf1 in mRNA deadenylation and decay in trypanosomes and human cells

Angela Schwede1, Louise Ellis, Julia Luther

  • 1Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.

Nucleic Acids Research
|April 30, 2008
PubMed

Insights

The study reveals that Caf1, a key deadenylation enzyme, is crucial for mRNA decay in both humans and trypanosomes. Its depletion impairs deadenylation, affecting RNA stability and cell survival.

Area of Science:

  • Molecular Biology
  • Eukaryotic Gene Regulation

Background:

  • The Ccr4/Caf1/Not complex regulates mRNA deadenylation.
  • Caf1 and Ccr4 subunits possess potential deadenylating enzyme activity.

Purpose of the Study:

  • Investigate the roles of Ccr4 and Caf1 in mRNA deadenylation.
  • Compare these roles in early-diverging eukaryotes: humans and trypanosomes.

Main Methods:

  • Characterized the Ccr4/Caf1/Not complex in Trypanosoma brucei.
  • Depleted Caf1 homologues in both T. brucei and human cells.
  • Assessed deadenylation and mRNA degradation rates.

Main Results:

  • Identified a trypanosome complex with CAF1, NOT1, NOT2, NOT5, DHH1, and a Caf130 homologue; no Ccr4 homologue found.
  • Trypanosome CAF1 exhibits deadenylation activity and is essential for cell viability.
  • Depletion of Caf1 homologues in both species inhibited bulk RNA deadenylation and increased poly(A) tail length.
  • Simultaneous depletion of human Caf1 isozymes impaired reporter mRNA degradation.

Conclusions:

  • Caf1 is an essential deadenylase in trypanosomes, vital for mRNA turnover and cell survival.
  • Caf1 plays a conserved, critical role in mRNA deadenylation and regulation across eukaryotes.
  • The absence of a Ccr4 homologue in trypanosomes suggests functional divergence within the Ccr4/Caf1/Not complex.

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