Shubin, A. V. | Search bioRxiv

bioRxiv2024

Irreproducibility of transgenerational learned pathogen-aversion response in C. elegans

Here we report our attempt to replicate reports of transgenerational epigenetic inheritance in Caenorhabditis elegans. Published results from multiple laboratories show that C. elegans adults and their F1 embryos exposed to the pathogen Pseudomonas aeruginosa show pathogen aversion behavior and a pathogen exposure-dependent increase in daf-7/TGF{beta} reporter gene expression. However, results from one group show persistence of the aversion behavior and elevated daf-7 expression in the F2, F3, and F4 generations. In contrast, we failed to consistently detect either the pathogen avoidance response or elevated daf-7 expression beyond the F1 generation. We did confirm that the dsRNA transport proteins SID-1 and SID-2 are required for the intergenerational (F1) inheritance of pathogen avoidance, but not for the F1 inheritance of elevated daf-7 expression. Furthermore, our reanalysis of RNA seq data provides additional evidence that this intergenerational inherited PA14 response may be mediated by small RNAs. The experimental methods are well-described, the source materials are readily available, including samples from the reporting laboratory, and we explored a variety of environmental conditions likely to account for lab-to-lab variability. None of these adjustments altered our results. We conclude that this example of transgenerational inheritance lacks robustness, confirm that the intergenerational avoidance response, but not the elevated daf-7p::gfp expression in F1 progeny, requires sid-1 and sid-2, and identify candidate siRNAs and target genes that may mediate this intergenerational response.

genetics↗

bioRxiv2021

Individual expression of hepatitis A virus 3C protease induces ferroptosis in human cells in vitro

Regulated cell death (RCD) is a fundamental process common to nearly all living beings and essential for the development and tissue homeostasis in animals and humans. A wide range of molecules can induce RCD including a number of viral proteolytic enzymes. To date, numerous data indicate that picornaviral 3C proteases can induce RCD. In most reported cases, these proteases induce classical caspase-dependent apoptosis. In contrast, the human hepatitis A virus 3C protease (3Cpro) has recently been shown to cause caspase-independent cell death accompanied by previously undescribed features. Here, we describe the 3Cpro effect on human cells in vitro and demonstrate that the enzyme induces ferroptosis which is mediated by iron ions and cause oxidative stress in the cells. This is the first demonstration that proteolytic enzyme can induce ferroptosis, the recently discovered and actively studied type of RCD.

cell biology↗