Drosophila cap-binding protein eiF4EHP promotes translation via a 3’UTR-dependent mechanism under hypoxia and contributes to fruit fly adaptation to oxygen variations

Autor: Manfei Liang, Clara Hody, Vanessa Yammine, Romuald Soin, Yuqiu Sun, Xing Lin, Xiaoying Tian, Romane Meurs, Camille Perdrau, Nadège Delacourt, Fabienne Andris, Louise Conrard, Véronique Kruys, Cyril Gueydan
Rok vydání: 2022
DOI: 10.1101/2022.07.20.500870
Popis: Hypoxia induces profound modifications in gene expression program enabling eukaryotic cells to adapt to lowered ATP supply resulting from the blockade of oxidative phosphorylation. One major consequence of oxygen deprivation is the massive repression of protein synthesis, leaving a limited set of mRNAs to be translated. D. melanogaster is strongly resistant to oxygen fluctuations, however the mechanisms allowing specific mRNA to be translated in hypoxia are still unknown. Here, we show that Ldh mRNA encoding lactate dehydrogenase is highly translated in hypoxia by a mechanism involving its 3’ untranslated region. Furthermore, we identified the cap-binding protein eiF4HP as a main factor involved in 3’UTR-dependent translation under hypoxia. In accordance with this observation, we show that eiF4EHP is necessary for Drosophila development under low oxygen concentrations and contributes to Drosophila mobility after hypoxic challenge. Altogether, our data bring new insight into mechanisms contributing to Drosophila adaptation to oxygen variations.
Databáze: OpenAIRE