Abstract
Although a CCTG expansion in the gene encoding the zinc knuckle protein CNBP causes a common form of muscular dystrophy, the function of both human CNBP and its putative budding yeast ortholog Gis2 remain poorly understood. Here we report the protein interactions of Gis2 and the subcellular locations of both Gis2 and CNBP. We found that Gis2 exhibits RNA-dependent interactions with two proteins involved in mRNA recognition, the poly(A) binding protein and the translation initiation factor eIF4G. We show that Gis2 is a component of two large RNA-protein granules, processing bodies and stress granules, which contain translationally repressed mRNAs. Consistent with a functional ortholog, CNBP also associates with the poly(A) binding protein and accumulates in stress granules during arsenite treatment of human cells. These results implicate both Gis2 and CNBP in mRNA handling during stress.
Highlights
The numerous conserved RNA-binding proteins in eukaryotic cells influence the metabolism, structure and function of their target RNAs in diverse ways
Several other proteins were linked to translation initiation, such as the cap-binding protein eIF4E [30], or mRNA stability, such as Xrn1, the major 59 to 39 exoribonuclease that carries out mRNA decay [31]
Our experiments demonstrate that S. cerevisiae Gis2 interacts with translation initiation factors and is a novel component of P-bodies and stress granules
Summary
The numerous conserved RNA-binding proteins in eukaryotic cells influence the metabolism, structure and function of their target RNAs in diverse ways The importance of these proteins for normal cell physiology is underscored by the increasing realization that defects in RNA-binding proteins underlie a range of human diseases [1,2,3]. Despite the progress that has been made in characterizing RNA-binding proteins, grouping them into families based on their structural domains, and identifying their RNA targets and cellular roles, the functions of many conserved and clinically important RNA-binding proteins remain poorly understood. One such RNA-binding protein is the cellular nucleic acid binding protein CNBP ( called ZNF9, zinc finger nine). In support of a key cellular role, CNBP is essential for mouse development [11], and likely orthologs exist in many animal species and in fungi [12,13,14,15]
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