IRES-mediated translation of the pro-apoptotic Bcl2 family member PUMA

Translation
Atossa ShaltoukiCrystal M Weyman

Abstract

The proapoptotic Bcl-2 family member PUMA is a critical regulator of apoptosis. We have previously shown that PUMA plays a pivotal role in the apoptosis associated with skeletal myoblast differentiation and that a MyoD-dependent mechanism is responsible for the increased expression of PUMA in these cells. Herein, we report that the increased expression of PUMA under these conditions involves regulation at the level of translation. Specifically, we have found that the increase in PUMA protein levels occurs under conditions of decreased total protein synthesis, eIF2-alpha phosphorylation and hypophosphorylation of eIF4E-BP, suggesting that PUMA translation is proceeding via an alternative initiation mechanism. Polyribosome analysis of PUMA mRNA further corroborated this suggestion. A combination of in vitro and ex vivo (cellular) approaches has provided evidence suggesting that PUMA mRNA 5'UTR harbors an Internal Ribosome Entry Site (IRES) element. Using mono- and bi-cistronic reporter constructs, we have delineated an mRNA fragment that allows for cap-independent translation in vitro and ex vivo (in skeletal myoblasts) in response to culture in differentiation media (DM), or in response to treatment with the DNA-damaging agent, ...Continue Reading

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Citations

Jan 14, 2017·Journal of Nucleic Acids·Divya Khandige SharmaNehal Thakor
Jun 3, 2021·International Journal of Molecular Sciences·Guus Gijsbertus Hubert van den AkkerTim Johannes Maria Welting

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Methods Mentioned

BETA
immunoprecipitation
PCR
density gradient fractionation
dissection
transfection
electrophoresis
scraping

Software Mentioned

PeakTrak
mFold

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