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  Multiple mechanisms repress N-Bak mRNA translation in the healthy and apoptotic neurons

Jakobson, M., Jakobson, M., Llano, O., Palgi, J., & Arumae, U. (2013). Multiple mechanisms repress N-Bak mRNA translation in the healthy and apoptotic neurons. CELL DEATH & DISEASE, 4: e777. doi:10.1038/cddis.2013.297.

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Jakobson, M.1, Autor
Jakobson, M.2, Autor           
Llano, O.1, Autor
Palgi, J.1, Autor
Arumae, U.1, Autor
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Schlagwörter: DEPRIVED SYMPATHETIC NEURONS; OPEN READING FRAMES; STRESS GRANULES; CYTOCHROME-C; P-BODIES; BH3-ONLY PROTEINS; GENE-EXPRESSION; CELL-DEATH; MITOCHONDRIA; INITIATIONN-Bak; translational repression; PTC; uORF; UTR; NMTR;
 Zusammenfassung: N-Bak is a neuron-specific BH3-only splice variant of pro-apoptotic Bcl-2 family member Bak. We have shown that its mRNA is stable in the neurons, whereas the protein cannot be detected by antibodies, suggesting a strong translational arrest of the mRNA. Here we identify two regulatory elements in the N-Bak mRNA that significantly repress translation in the luciferase reporter assay: an upstream open reading frame in the 5'-untranslated region (UTR) and naturally spliced exon-exon junction downstream of the premature translation termination codon in the 3'UTR. We also show that N-Bak mRNA is stored in granular structures in the sympathetic neurons and stays in these granules during intrinsic apoptosis. Finally, we confirm the absence of N-Bak protein by quantitative mass spectrometry analysis in the healthy, apoptotic or stressed sympathetic and cortical neurons. We conclude that N-Bak mRNA is translationally repressed by multiple mechanisms, and the protein does not participate in the classical apoptosis or cellular stress response.

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Sprache(n): eng - English
 Datum: 2013-08
 Publikationsstatus: Online veröffentlicht
 Seiten: 10
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: Expertenbegutachtung
 Identifikatoren: ISI: 000324146000034
DOI: 10.1038/cddis.2013.297
 Art des Abschluß: -

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Titel: CELL DEATH & DISEASE
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND : NATURE PUBLISHING GROUP
Seiten: - Band / Heft: 4 Artikelnummer: e777 Start- / Endseite: - Identifikator: ISSN: 2041-4889