Ataxin-2 interacts with the DEAD/H-box RNA helicase DDX6 and interferes with P-bodies and stress granules

被引:266
作者
Nonhoff, Ute [1 ]
Ralser, Markus [1 ]
Welzel, Franziska [1 ]
Piccini, Ilaria [1 ]
Balzereit, Daniela [1 ]
Yaspo, Marie-Laure [1 ]
Lehrach, Hans [1 ]
Krobitsch, Sylvia [1 ]
机构
[1] Max Planck Inst Mol Genet, D-14195 Berlin, Germany
关键词
D O I
10.1091/mbc.E06-12-1120
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
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收藏
页码:1385 / 1396
页数:12
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