Fig. 6: The oxygen-sensitive RBP network regulates hypoxia sensitivity across species.
From: A network of RNA-binding proteins controls translation efficiency to activate anaerobic metabolism
a Protein sequence similarity of hypoxia-activated RBPs across species. High protein sequence similarity (compared to the human homolog, first column) is indicated by dark blue coloring, and low protein similarity by light blue/white coloring (see legend on bottom right corner of panel). Analysis using the normalized phylogenetic profiling algorithm identified evidence suggesting co-evolution between HuR and hnRNP A2/B1 (Pearson r = 0.93, z score = 8.41). b Analysis of published RBP interactome data using the BioGRID bioinformatics resource reveals conserved protein interactions (indicated in green) between hypoxia-adaptive RBPs. An interaction is considered conserved if observed in human, mouse, fly, nematode, and at least one plant species. Measurements of c, e lactate and d, f ATP production in C. elegans subjected to c, d 1% O2 or e, f 0.1% O2. Color scheme: red, normoxia; blue, hypoxia. Data represent mean of triplicate measurements from a representative experiment. Three independent experiments (n = 3) were performed with similar results. g Translation efficiencies of glycolytic effectors in hypoxic (0.1% O2) C. elegans that contain wild-type (N2) or mutant homologs of HuR (exc-7, strain NJ683) or hnRNP A2/B1 (H28G03.1, strain VC3835), as determined by qRT-PCR of ribosome density fractions. Asterisk denotes statistical significance calculated using two-sided Student’s t-tests compared to wild-type control. Exact p values: NJ683: fgt-1 (p = 0.02), hxk-2 (p = 0.04), gpi-1 (p = 0.02), pfk-1.1 (p = 0.03), aldo-1 (p = 0.002); VC3835: fgt-1 (p = 0.03), hxk-2 (p = 0.04), gpi-1 (p = 0.003), aldo-1 (p = 0.009), gpd-1 (p = 0.02), enol-1 (p = 0.004). Data represent mean ± SEM (error bars) of three independent experiments (n = 3). h Measurements of normoxic and hypoxic (0.1% O2) death for adult (day 1 at the start of treatment) C. elegans that contain wild-type (N2) or mutant homologs of HuR (strains NJ683 and VC176) or hnRNP A2/B1 (strain VC3835). Statistical significance was calculated using two-sided Student’s t-tests compared to wild-type control. Exact p values are indicated in the figure. Data represent mean ± SEM (error bars) of four independent experiments (n = 4; total number of worms for N2, NJ683, VC176, VC3835: 927, 860, 753, 731, respectively). Source data are provided as a Source data file.
