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Identification of the TXNIP IRES and characterization of the impact of regulatory IRES trans-acting factors

ABSTRACT: Translation is a tightly regulated and is predominantly controlled at the level of its initiation. Initiation 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 searched for new IRESes by identifying 5’ untranslated regions (UTRs) bound by the ITAF hnRNPA1. Using a PAR-iCLIP approach, we found the mRNA of thioredoxin interacting protein (TXNIP) bound by 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, FBP3, and GEMIN5 emerged as functional ITAFs. Finally, we found that the TXNIP IRES-inhibitory effect of PTB was dominant over the activating effect of FBP3, while it succumbed to the stimulatory function of GEMIN5. 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE97159 | GEO | 2018/01/23

REPOSITORIES: GEO

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