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Eri1 degrades the stem-loop of oligouridylated histone mRNAs to induce replication-dependent decay

Kai P Hoefig1, Nicola Rath, Gitta A Heinz

  • 1Institute of Molecular Immunology, Helmholtz Zentrum München, München, Germany.

Nature Structural & Molecular Biology
|December 4, 2012
PubMed

Insights

The exoRNase Eri1 enzyme

Area of Science:

  • Molecular Biology
  • RNA Metabolism
  • Gene Regulation

Background:

  • The exoRNase Eri1 has known roles in RNA interference and rRNA processing.
  • Its interaction with histone mRNA stem-loops was observed but functionally uncharacterized.
  • Histone mRNA degradation is crucial for cell cycle regulation and typically occurs post-S phase.

Purpose of the Study:

  • To elucidate the functional role of the exoRNase Eri1 in histone mRNA degradation.
  • To understand the mechanism by which Eri1 processes histone mRNAs.
  • To investigate the role of 3' end modifications in histone mRNA decay.

Main Methods:

  • Analysis of Eri1-deficient mouse cells.
  • Biochemical assays to study Eri1 activity on histone mRNA substrates.
  • Investigation of the interaction between Eri1 and the Lsm1-7 heteroheptamer.

Main Results:

  • Eri1 deficiency leads to the accumulation of oligouridylated histone mRNAs.
  • Eri1 trims histone mRNAs but stalls at the double-stranded stem-loop.
  • Oligouridylation of histone mRNA creates a binding site for the Lsm1-7 complex, which recruits Eri1 to facilitate stem-loop processing.
  • This interaction enables stepwise degradation of the histone mRNA stem-loop.

Conclusions:

  • 3' end oligouridylation of histone mRNAs is a key trigger for their degradation.
  • The Lsm1-7 complex acts as a scaffold, bringing Eri1 to the histone mRNA stem-loop for processing.
  • Eri1's nucleolytic activity, in conjunction with oligouridylation and Lsm1-7, provides a mechanism for regulated histone mRNA decay.

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