Abstract
By using RNA-immunoprecipitation assay following next-generation sequencing, a group of cell cycle-related genes targeted by hnRNP Q1 were identified, including Aurora-A kinase. Overexpressed hnRNP Q1 can upregulate Aurora-A protein, but not alter the mRNA level, through enhancing the translational efficiency of Aurora-A mRNA, either in a cap-dependent or -independent manner, by interacting with the 5′-UTR of Aurora-A mRNA through its RNA-binding domains (RBDs) 2 and 3. By ribosomal profiling assay further confirmed the translational regulation of Aurora-A mRNA by hnRNP Q1. Overexpression of hnRNP Q1 promotes cell proliferation and tumor growth. HnRNP Q1/ΔRBD23-truncated mutant, which loses the binding ability and translational regulation of Aurora-A mRNA, has no effect on promoting tumor growth. The expression level of hnRNP Q1 is positively correlated with Aurora-A in colorectal cancer. Taken together, our data indicate that hnRNP Q1 is a novel trans-acting factor that binds to Aurora-A mRNA 5′-UTRs and regulates its translation, which increases cell proliferation and contributes to tumorigenesis in colorectal cancer.
Highlights
Heterogeneous nuclear ribonucleoproteins are a large group of RNA-binding proteins that associate with the heterogeneous nuclear RNAs transcribed by RNA polymerase II in eukaryotic cells
HnRNP Q members consist of one acidic domain (AcD) at the N-terminus that is involved in protein– protein interaction, three RNA-binding domains (RBDs) in the central region and one RGG box at the C-terminus for binding to RNA
The results indicated that Heterogeneous nuclear ribonucleoproteins (hnRNPs) Q1 is overexpressed in colorectal cancer cell lines than the normal colon cell line CRL1790 (Figure 1a)
Summary
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a large group of RNA-binding proteins that associate with the heterogeneous nuclear RNAs (hnRNAs) transcribed by RNA polymerase II in eukaryotic cells. HnRNP Q can act as a positive regulator of the IRES.[12,15] some reports indicate that hnRNP Q can target the 3′-UTR of mRNAs and disrupt poly(A)-binding protein (PABP)-mediated circular mRNA formation to repress cap-dependent translation.[14,16,17] the role of hnRNP Q in regulating translation might depend on the binding sites of mRNAs. A previous report indicated that hnRNP Q is involved in the maintenance of cell proliferation in colon cancer cells by associating with galectin[3], but the underlying mechanism is still unclear.[18] the specific target genes regulated by hnRNP Q have not been completely identified. We selected Aurora kinase A (AURKA) for the following study because of its roles in mitotic entry and tumorigenic capacity.[20]
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