A widespread family of heat-resistant obscure (Hero) proteins protect against protein instability and aggregation
(A) Cell growth assay of HEK293T cells acutely knocked out for the indicated genes. Four days after transfection of gRNA, the numbers of the cells were measured by a coloring assay. Knockout of Hero13 and Hero7 reduced the cell proliferation. Data represent means ± SD of the cell numbers from 8 independent wells. (B) Whole-body knockdown phenotypes in Drosophila. Knockdown of endogenous fly Hero proteins were performed by two independent RNAi strains (GD and KK lines). Whole-body depletion of Hero proteins often caused lethality, suggesting that Hero proteins play essential roles in Drosophila early development. Note that we used two different GD lines for CG3760. We observed the same phenotype for at least two independent crosses per each genotype. (C) Survival plots of Drosophila. Whole-body overexpression of CG12384 or CG14818 elongated life spans, compared to the wild type. (D) Summary of life span analysis in Drosophila. Whole-body overexpression of Hero proteins except human Hero11 significantly elongated life spans. (E) A model for the modes of action of chaperones and Hero proteins. Chaperones usually act on the inactive/denatured state of their client proteins and actively reverse them to the functional state by using ATP, while Hero proteins likely act on the functional state of their client proteins and protect them from lapsing into the inactive/denatured state in an ATP-independent manner. The numerical data pertaining to this figure can be found in S1 Data file. gRNA, guide RNA; Hero, heat-resistant obscure; RNAi, RNA interference; WT, wild-type; YFP, yellow fluorescent protein.