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Rate of Protein Synthesis Under Hypometabolic Conditions: The Down and Up and Down
Author(s) -
Fähling Michael,
Steege Andreas,
Mrowka Ralf,
Martinka Peter,
Perlewitz Andrea,
Persson Pontus Börje,
Thiele Bernd Joachim
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1174.12
Subject(s) - gene expression , polysome , protein biosynthesis , messenger rna , hypoxia (environmental) , gene , translation (biology) , microbiology and biotechnology , rna , biology , phosphorylation , regulation of gene expression , chemistry , kinase , biochemistry , oxygen , ribosome , organic chemistry
The first striking cellular response to hypoxia (1% oxygen) is the suppression of energy consuming processes, including gene expression. mRNA translation is of high energy cost and consequently undergoes a rapid inhibition following hypoxia. This translational arrest is mediated by several kinases which phosphorylate, e.g., translation elongation factors. The evaluation of reporter gene assays reveals a time dependent, multi‐phase response in the hypoxic adaptation of overall gene expression: We found that the short term suppression of protein synthesis rate under hypoxia can be rescued up to 18 h, but then comes down again under prolonged conditions. In the “rescue”‐phase, polysomal gradient analyses indicate a dissociation of polysomes, which seems to be compensated by a general shift of mRNAs into polysomal fractions. Under long term hypoxia the inhibition of gene expression is accompanied by the lack of small RNA species, e.g., tRNAs. Nevertheless, specific mRNAs can circumvent these inhibitory processes, showing an increased gene expression rate against the overall trend. RNA binding proteins such as nucleolin seems to be crucial for this selection. The findings indicate new possible pathways, with respect to short term or prolonged hypoxia, which assure a constant or even elevated gene expression rate under conditions of metabolic rate depression.