Abstract
The function of ribosome binding protein 1 (RRBP1) is regulating the transportation and secretion of some intracellular proteins in mammalian cells. Transcription of RRBP1 is induced by various cytokines. However, few studies focused on the process of RRPB1 mRNA translation. The RRBP1 mRNA has a long 5′ untranslated region that potentially formed a stable secondary structure. In this study, we show that the 5′ UTR of RRBP1 mRNA contains an internal ribosome entry site (IRES). Moreover, the RRBP1 expression is induced by chemotherapeutic drug paclitaxel or adriamycin in human hepatocellular carcinoma cells and accompanied with the increased expression of La autoantigen (La), which binds to RRBP1 IRES element and facilitates translation initiation. Interestingly, we found IRES-mediated RRBP1 translation is also activated during serum-starvation condition which can induce cytoplasmic localization of La. After mapping the entire RRBP1 5′ UTR, we determine the core IRES activity is located between nt-237 and -58. Furthermore, two apical GARR loops within the functional RRBP1 IRES elements may be important for La binding. These results strongly suggest an important role for IRES-dependent translation of RRBP1 mRNA in hepatocellular carcinoma cells during cellular stress conditions.
Highlights
In eukaryotic cells, expression level of proteins is determined and regulated by mRNA translation according to a ribosome scanning mechanism [1]
To investigate whether the expression of RRBP1 was affected during cellular stress, we measured the endogenous protein and mRNA levels of RRBP1 in human hepatocellular carcinoma cells (Bel7402) treated with paclitaxel (PTX) and adriamycin (ADM), which are applied as chemotherapy drugs in cancer
We found the highly expression of RRBP1 induced by 0.4 μg/mL PTX resulted in an elongated morphology in Bel7402 cells compared to the untreated cells
Summary
Expression level of proteins is determined and regulated by mRNA translation according to a ribosome scanning mechanism [1]. In this mechanism, the 40S ribosomal subunit conjugating with various initiation factors recognizes the methyl cap structure on the 51 end of a mRNA and scans the transcript until encountering the initiator methionine codon in the proper context for translation [2]. Some researchers reported the increase expression of RRBP1 protein in some tumor cells, indicated the great role of RRBP1 for survival, malignancy maintenance, and adaptation to ER stress in tumor cells. This study was beneficial to gain a better understanding of the IRES-mediated RRBP1 translation mechanism and provide an effective method for cancer therapy
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