BACKGROUND AND PURPOSE: Protein synthesis rates are greatly reduced under hypoxic conditions as a consequence of an overall inhibition of mRNA translation. Certain specific mRNA species have the ability to escape this general translational repression. At the cellular level this results in differential protein expression during hypoxic conditions. The objective of this study was to characterize the translational regulation of the postulated HIF-1alpha antagonist Cited2. MATERIALS AND METHODS: DU145 prostate carcinoma cells and mouse embryonic fibroblasts with a homozygous knock-in mutation for eIF2alpha (S51A) or wild-type eIF2alpha were exposed to severe hypoxia after which both total mRNA and efficiently translated mRNA were isolated. Quantitative RT-PCR was used to measure and compare changes in transcription (total mRNA) with changes in translation (efficiently translated mRNA fraction). RESULTS: We show using HIF-1alpha null MEF cells that transcriptional induction of Cited2 during hypoxia is dependent on HIF-1alpha. Although global mRNA translation is inhibited during hypoxia Cited2 mRNA remains efficiently translated. An evolutionary conserved upstream open reading frame (uORF) in the 5'UTR of Cited2 did not stimulate translation in an eIF2alpha dependent manner during hypoxia. CONCLUSIONS: Selective translation Cited2 by an eIF2alpha independent mechanism establishes a link between translation and HIF-1 dependent transcription during hypoxia.
BACKGROUND AND PURPOSE: Protein synthesis rates are greatly reduced under hypoxic conditions as a consequence of an overall inhibition of mRNA translation. Certain specific mRNA species have the ability to escape this general translational repression. At the cellular level this results in differential protein expression during hypoxic conditions. The objective of this study was to characterize the translational regulation of the postulated HIF-1alpha antagonist Cited2. MATERIALS AND METHODS: DU145 prostate carcinoma cells and mouse embryonic fibroblasts with a homozygous knock-in mutation for eIF2alpha (S51A) or wild-type eIF2alpha were exposed to severe hypoxia after which both total mRNA and efficiently translated mRNA were isolated. Quantitative RT-PCR was used to measure and compare changes in transcription (total mRNA) with changes in translation (efficiently translated mRNA fraction). RESULTS: We show using HIF-1alpha null MEF cells that transcriptional induction of Cited2 during hypoxia is dependent on HIF-1alpha. Although global mRNA translation is inhibited during hypoxiaCited2 mRNA remains efficiently translated. An evolutionary conserved upstream open reading frame (uORF) in the 5'UTR of Cited2 did not stimulate translation in an eIF2alpha dependent manner during hypoxia. CONCLUSIONS: Selective translation Cited2 by an eIF2alpha independent mechanism establishes a link between translation and HIF-1 dependent transcription during hypoxia.
Authors: Claudia Fritsch; Alexander Herrmann; Michael Nothnagel; Karol Szafranski; Klaus Huse; Frank Schumann; Stefan Schreiber; Matthias Platzer; Michael Krawczak; Jochen Hampe; Mario Brosch Journal: Genome Res Date: 2012-08-09 Impact factor: 9.043
Authors: Jonas J Staudacher; Isabel S Naarmann-de Vries; Stefanie J Ujvari; Bertram Klinger; Mumtaz Kasim; Edgar Benko; Antje Ostareck-Lederer; Dirk H Ostareck; Anja Bondke Persson; Stephan Lorenzen; Jochen C Meier; Nils Blüthgen; Pontus B Persson; Alexandra Henrion-Caude; Ralf Mrowka; Michael Fähling Journal: Nucleic Acids Res Date: 2015-03-08 Impact factor: 16.971
Authors: Mohammed R Alzahrani; Bo-Jhih Guan; Leah L Zagore; Jing Wu; Chien-Wen Chen; Donny D Licatalosi; Kristian E Baker; Maria Hatzoglou Journal: PLoS One Date: 2022-08-10 Impact factor: 3.752