Long non-coding RNAs regulate heavy metal-induced apoptosis in embryo-derived cells

Area of Science:

• Environmental toxicology
• Molecular biology
• Genomics

Background:

• Heavy metal pollution poses a significant threat to ecosystems and animal health.
• Research on heavy metal toxicity mechanisms has primarily focused on protein-coding genes, overlooking the role of long non-coding RNAs (lncRNAs).
• The regulatory functions of lncRNAs in heavy metal stress response remain largely unexplored.

Purpose of the Study:

• To investigate the role of lncRNAs in cellular responses to heavy metal stress.
• To identify lncRNAs induced by heavy metals in an insect cell model.
• To elucidate the regulatory mechanisms underlying heavy metal toxicity involving lncRNAs.

Main Methods:

• Development of an insect embryo cell model (Drosophila S2 cells) for studying metal toxicity.
• Genome-wide screening and functional characterization of lncRNAs and mRNAs.
• Construction of lncRNA-mRNA co-expression networks and pathway enrichment analysis.
• Functional validation of a specific lncRNA (CR44138) using expression interference.

Main Results:

• Identification of 4894 lncRNAs, including 1410 novel ones, induced by four different heavy metals.
• Discovery of 41 lncRNAs and 328 mRNAs commonly induced by all tested heavy metals.
• Activation of detoxification, circadian rhythm, and apoptosis pathways in response to heavy metal stress.
• Upregulation of lncRNA CR44138 in heavy metal-exposed cells, linked to apoptosis; CR44138 exacerbates heavy metal-induced apoptosis.

Conclusions:

• lncRNAs play a significant role in regulating cellular responses to heavy metal stress.
• The study provides a foundation for understanding novel regulatory mechanisms of heavy metal toxicity.
• lncRNAs, such as CR44138, represent potential diagnostic biomarkers for heavy metal pollutant effects.