La Autoantigen Induces Ribosome Binding Protein 1 (RRBP1) Expression through Internal Ribosome Entry Site (IRES)-Mediated Translation during Cellular Stress Condition

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.

Repurposing Potential of Riluzole as an ITAF Inhibitor in mTOR Therapy Resistant Glioblastoma

“…Our data demonstrate that riluzole can display synergistic anti-GBM effects with mTOR inhibitors (see Figure 5C) and recent data have demonstrated that riluzole synergizes with the chemotherapeutic paclitaxel in triple-negative breast cancers [53]. It is well known that chemotherapeutically induced cellular stress can activate IRES-mediated protein synthesis of various transcripts, including the aryl hydrocarbon receptor, ATF2, ribosome binding protein 1, c-myc and β-catenin [54][55][56][57][58]. While c-myc IRES-dependent translation is mediated via hnRNP A1, it is tempting to speculate that these other IRES containing mRNAs may also be regulated via hnRNP A1 activity and that these compounds may be utilized to identify other transcripts subject to hnRNP A1-mediated IRES regulation.…”

Expression and significance of RRBP1 in esophageal carcinoma

“…RRBP1, an endoplasmic reticulum membrane protein, is mainly located on the endoplasmic reticulum membrane and plays an important role in the transportation and secretion of nascent proteins. 9 , 11 , 15 Moreover, RRBP1 is crucial for the terminal differentiation of secretory tissues and the procollagen biosynthesis of secretory tissues. 16 – 19 Recently, RRBP1 has been reported to be connected to the regulation of unfolded protein response signaling molecules and the accumulation of perinuclear autophagosomes of cancer cells.…”

Paclitaxel-mediated human aryl hydrocarbon receptor mRNA translation by an internal ribosomal entry site-dependent mechanism

“…Renilla luciferase (first cistron, RL) and firefly luciferase (second cistron, FL) was described previously (31,32). To obtain plasmids pR-NRF-F and pR-AHR-F, we inserted the 5'-UTRs of AHR and NRF which were synthesized by Sangon Biotech.…”

“…To determine if the AHR 5'-UTR contains an IRES, we employed the dicistronic reporter plasmid pRF (31). The dicistronic construct contains a Renilla luciferase (RL) open reading frame (ORF) and a firefly luciferase (FL) ORF that are separated by an intercistronic region.…”