Ataxin-2 interacts with the DEAD/H-box RNA helicase DDX6 and interferes with P-bodies and stress granules.
Tight control of translation is fundamental for eukaryotic cells, and deregulation of proteins implicated contributes to numerous human diseases. The neurodegenerative disorder spinocerebellar ataxia type 2 is caused by a trinucleotide expansion in the SCA2 gene encoding a lengthened polyglutamine stretch in the gene product ataxin-2, which seems to be implicated in cellular RNA-processing pathways and translational regulation. Here, we substantiate a function of ataxin-2 in such pathways by demonstrating that ataxin-2 interacts with the DEAD/H-box RNA helicase DDX6, a component of P-bodies and stress granules, representing cellular structures of mRNA triage. We discovered that altered ataxin-2 levels interfere with the assembly of stress granules and cellular P-body structures. Moreover, ataxin-2 regulates the intracellular concentration of its interaction partner, the poly(A)-binding protein, another stress granule component and a key factor for translational control. Thus, our data imply that the cellular ataxin-2 concentration is important for the assembly of stress granules and P-bodies, which are main compartments for regulating and controlling mRNA degradation, stability, and translation.
Nonhoff
Ute
U
Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Ralser
Markus
M
Welzel
Franziska
F
Piccini
Ilaria
I
Balzereit
Daniela
D
Yaspo
Marie-Laure
ML
Lehrach
Hans
H
Krobitsch
Sylvia
S
D000067528:Ataxins; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000648:ultrastructure; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008830:Microbodies / Q000378:metabolism / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*
D000067528:Ataxins; D009419:Nerve Tissue Proteins; D039102:Poly(A)-Binding Proteins; D011518:Proto-Oncogene Proteins; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases