Identification of the TXNIP IRES and characterization of the impact of regulatory IRES trans-acting factors |
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Authors: | Sebastian Lampe Michael Kunze Anica Scholz Thilo F Brauß Sofia Winslow Stefan Simm Mario Keller Juliana Heidler Ilka Wittig Bernhard Brüne Tobias Schmid |
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Institution: | 1. Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany;2. Department of Molecular Cell Biology of Plants, Faculty of Biosciences, Goethe-University Frankfurt, 60438 Frankfurt, Germany;3. Functional Proteomics, SFB 815 Core Unit, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany |
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Abstract: | Translation is a tightly regulated process and is predominantly controlled at the level of its initiation. Translation initiation mostly occurs in a cap-dependent manner. Under stress conditions when cap-dependent translation is hampered, internal ribosome entry sites (IRESes) allow for cap-independent translation of certain mRNAs. IRES-dependent translation is commonly regulated by RNA-interacting proteins, known as IRES trans-acting factors (ITAFs). In the present study, we found the 5′ untranslated region (UTR) of the thioredoxin-interacting protein (TXNIP) mRNA to be bound by the ITAF hnRNPA1. Upon verification of an IRES element within the 5′UTR of TXNIP, we determined additional interacting proteins, which predominantly appeared to interact with the IRES-regulatory second half of the 5′UTR. Amongst these PTB emerged as an inhibitory ITAF, whereas FBP3 and GEMIN5 appeared to contain TXNIP IRES-enhancing properties. In summary, we identified and characterized a novel IRES within the 5′UTR of TXNIP, which is regulated by the ITAFs PTB, FBP3, and GEMIN5. |
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Keywords: | eIF eukaryotic initiation factor FBP3 far upstream element-binding protein 3 GEMIN5 gem nuclear organelle associated protein 5 hnRNPA1 heterogeneous ribonucleoprotein A1 ITAF IRES internal ribosome entry site PAR-iCLIP photoactivatable ribonucleoside enhanced individual nucleotide resolution cross linking and immunoprecipitation PTB polypyrimidine tract-binding protein TXNIP thioredoxin-interacting protein UTR untranslated region Cap-independent translation Internal ribosome entry site RNA-binding protein TXNIP |
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