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

Abstract

Ataxin-2 is a cytoplasmic protein, product of the ATXN2 gene, whose deficiency leads to obesity, while its gain-of-function leads to neural atrophy. Ataxin-2 affects RNA homeostasis, but its effects are unclear. Here, immunofluorescence analysis suggested that ataxin-2 associates with 48S pre-initiation components at stress granules in neurons and mouse embryonic fibroblasts, but is not essential for stress granule formation. Coimmunoprecipitation analysis showed associations of ataxin-2 with initiation factors, which were concentrated at monosome fractions of polysome gradients like ataxin-2, unlike its known interactor PABP. Mouse embryonic fibroblasts lacking ataxin-2 showed increased phosphorylation of translation modulators 4E-BP1 and ribosomal protein S6 through the PI3K-mTOR pathways. Indeed, human neuroblastoma cells after trophic deprivation showed a strong induction of ATXN2 transcript via mTOR inhibition. Our results support the notion that ataxin-2 is a nutritional stress-inducible modulator of mRNA translation at the pre-initiation complex.

• Authors: Isabel Lastres-Becker, David Nonis, Florian Eich, Michael Klinkenberg, Myriam Gorospe, Peter Kötter, Fabrice A C Klein, Nancy Kedersha, Georg Auburger
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1862 Issue 9 Pg. 1558-69 (09 2016) ISSN: 0006-3002 [Print] Netherlands
• PMID: 27240544 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier B.V. All rights reserved.

Chemical References

• Arsenites
• Ataxin-2
• Eukaryotic Initiation Factors
• RNA, Messenger
• Ribosomal Protein S6
• TOR Serine-Threonine Kinases
• arsenite

Topics

• Animals
• Arsenites (toxicity)
• Ataxin-2 (antagonists & inhibitors, genetics, metabolism)
• Cell Line, Tumor
• Cells, Cultured
• Eukaryotic Initiation Factors (metabolism)
• Fibroblasts (metabolism)
• Gene Knockout Techniques
• HEK293 Cells
• Humans
• Mice
• Neurons (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Polyribosomes (metabolism)
• Protein Biosynthesis
• RNA, Messenger (genetics, metabolism)
• Rats
• Ribosomal Protein S6 (metabolism)
• Starvation (genetics, metabolism)
• Stress, Physiological
• TOR Serine-Threonine Kinases (metabolism)