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Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs
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Toeprinting Analysis of Translation Initiation Complex Formation on Mammalian mRNAs

Published on: May 10, 2018

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Mammalian ataxin-2 modulates translation control at the pre-initiation complex via PI3K/mTOR and is induced by

Isabel Lastres-Becker1, David Nonis1, Florian Eich1

  • 1Section of Molecular Neurogenetics, Dept. of Neurology, Building 89, 3rd floor, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt am Main, Germany.

Biochimica Et Biophysica Acta
|June 1, 2016
PubMed

Insights

Ataxin-2 protein modulates mRNA translation during nutritional stress. Its absence impacts translation factors via PI3K-mTOR pathways, affecting cellular homeostasis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Neuroscience

Background:

  • Ataxin-2, encoded by the ATXN2 gene, is a cytoplasmic protein implicated in both obesity (deficiency) and neural atrophy (gain-of-function).
  • Its precise role in RNA homeostasis and translation remains incompletely understood.

Purpose of the Study:

  • To elucidate the function of ataxin-2 in mRNA translation regulation, particularly under stress conditions.
  • To investigate the association of ataxin-2 with translation machinery and its role in stress granules.

Main Methods:

  • Immunofluorescence analysis to visualize ataxin-2 localization with stress granule components.
  • Coimmunoprecipitation assays to identify interacting protein partners.
  • Analysis of polysome gradients to determine ataxin-2's distribution within translation complexes.
  • Western blotting to assess phosphorylation of translation modulators in ataxin-2 deficient cells.

Main Results:

  • Ataxin-2 localizes with 48S pre-initiation complex components at stress granules but is not essential for their formation.
  • Ataxin-2 interacts with translation initiation factors and co-fractionates with monosomes.
  • Loss of ataxin-2 leads to increased phosphorylation of 4E-BP1 and S6 via PI3K-mTOR pathways.
  • ATXN2 transcript is upregulated by mTOR inhibition in response to trophic deprivation.

Conclusions:

  • Ataxin-2 functions as a nutritional stress-inducible modulator of mRNA translation.
  • It specifically impacts the pre-initiation complex, influencing translation rates under cellular stress.
  • These findings link ataxin-2 to cellular responses to nutrient availability and stress.
Keywords:
Amyotrophic lateral sclerosisDiabetes mellitusSpinocerebellar Ataxia type 2TORC1mRNA translation

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