Abstract
The Y-box proteins are multifunctional nucleic acid-binding proteins involved in various aspects of gene regulation. The founding member of the Y-box protein family, YB-1, functions as a transcription factor as well as a principal component of messenger ribonucleoprotein particles (mRNPs) in somatic cells. The nuclear level of YB-1 is well correlated with poor prognosis in many human cancers. Previously, we showed that a Y-box protein–associated acidic protein, YBAP1, which is identical to complement component 1, q subcomponent-binding protein (C1QBP, also called gC1qR, hyaluronan-binding protein 1 [HABP1] or ASF/SF2-associated protein p32), relieves translational repression by YB-1. Here we show that the nuclear localization of YB-1 harboring a point mutation in the cold shock domain was inhibited when co-expressed with YBAP1, whereas cytoplasmic accumulation of the wild-type YB-1 was not affected. We showed that YBAP1 inhibited the interaction between YB-1 and transportin 1. In the cytoplasm, YBAP1 affected the accumulation of YB-1 to processing bodies (P-bodies) and partially abrogated the mRNA stabilization by YB-1. Our results, indicating that YBAP1/C1QBP regulates the nucleo-cytoplasmic distribution of YB-1 and its cytoplasmic functions, are consistent with a model that YBAP1/C1QBP acts as an mRNP remodeling factor.
Highlights
Regulation of gene expression in eukaryotes depends on the functions of many proteins that bind DNA and RNA1
When the cell lysates were pretreated with RNase A, the amount of YBAP1 that co-precipitated with YB-1 increased, suggesting that YBAP1 interacts with YB-1 more efficiently when RNA is destroyed than when RNA is present
We showed that the first two alternating A/B regions (C2 region) of YB-1 were imported into the nucleus by transportin 1, and that YBAP1/C1QBP bound to the same region (Figs 1 and 3)
Summary
Regulation of gene expression in eukaryotes depends on the functions of many proteins that bind DNA and RNA1. The activities of these proteins are tightly regulated by multiple mechanisms, including association with ligands or other proteins, post-translational modification, and nucleocytoplasmic transport. YB-1 is a multifunctional DNA/RNA-binding protein with nuclear and cytoplasmic functions (reviewed by[6,7,8,9]). The CSD (~80 amino acids [aa] in length) is highly conserved in the Y-box protein family members, consisting of a five-stranded β barrel that includes the RNP-1 and RNP2 motifs essential for RNA binding. The C-terminal tail domain of Y-box proteins mediates their RNA-binding activities, and their protein–protein interactions. Our results suggest that the interaction with YBAP1/C1QBP regulates the localization and cytoplasmic activities of YB-1
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