Although tumor protein D52 (TPD52) family proteins were first identified nearly 20 years ago, their molecular regulatory mechanisms remain unclear. Therefore, we investigated the post-transcriptional regulation of TPD52 family genes. An RNA immunoprecipitation (RIP) assay showed the potential binding ability of TPD52 family mRNAs to several RNA-binding proteins, and an RNA degradation assay revealed that TPD52 is subject to more prominent post-transcriptional regulation than are TPD53 and TPD54. We subsequently focused on the 3′-untranslated region (3′-UTR) of TPD52 as a cis-acting element in post-transcriptional gene regulation. Several deletion mutants of the 3′-UTR of TPD52 mRNA were constructed and ligated to the 3′-end of a reporter green fluorescence protein gene. An RNA degradation assay revealed that a minimal cis-acting region, located in the 78-280 region of the 5′-proximal region of the 3′-UTR, stabilized the reporter mRNA. Biotin pull-down and RIP assays revealed specific binding of the region to T-cell intracellular antigen 1 (TIA-1) and TIA-1-related protein (TIAR). Knockdown of TIA-1/TIAR decreased not only the expression, but also the stability of TPD52 mRNA; it also decreased the expression and stability of the reporter gene ligated to the 3′-end of the 78-280 fragment. Stimulation of transforming growth factor-β and epidermal growth factor decreased the binding ability of these factors, resulting in decreased mRNA stability. These results indicate that the 78-280 fragment and TIA-1/TIAR concordantly contribute to mRNA stability as a cis-acting element and trans-acting factor(s), respectively. Thus, we here report the specific interactions between these elements in the post-transcriptional regulation of the TPD52 gene.
Tumor protein D52 expression is post-transcriptionally regulated by T-cell intercellular antigen (TIA) 1 and TIA-related protein via mRNA stability
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Hiromi Motohashi, Yoshiki Mukudai, Chihiro Ito, Kosuke Kato, Toshikazu Shimane, Seiji Kondo, Tatsuo Shirota; Tumor protein D52 expression is post-transcriptionally regulated by T-cell intercellular antigen (TIA) 1 and TIA-related protein via mRNA stability. Biochem J 15 May 2017; 474 (10): 1669–1687. doi: https://doi.org/10.1042/BCJ20160942
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