Reprograming gene expression in 'hibernating' C. elegans involves the IRE-1/XBP-1 pathway

Area of Science:

• Molecular biology
• Cellular stress response
• Cryobiology

Background:

• Animals hibernate and clinical hypothermia is used for medical treatments, but cellular cold survival mechanisms remain unclear.
• Global protein synthesis downregulation is a known cold adaptation strategy, but its role is debated.
• Understanding cold adaptation is crucial for fields ranging from evolutionary biology to emergency medicine.

Purpose of the Study:

• To investigate the molecular mechanisms of cellular cold survival.
• To determine how protein synthesis and gene expression are regulated during cold exposure.
• To identify key signaling pathways involved in cold adaptation.

Main Methods:

• Studied cold adaptation in the nematode *Caenorhabditis elegans*.
• Analyzed messenger RNA (mRNA) translation rates at low temperatures.
• Investigated gene expression patterns and the role of the unfolded protein response (UPR).
• Examined the IRE-1/XBP-1 signaling pathway's involvement in cold-induced gene expression.

Main Results:

• Most mRNAs in *C. elegans* continue translation in the cold, albeit at a reduced rate.
• Cold-specific gene expression is primarily regulated at the transcription level.
• The unfolded protein response (UPR), via the IRE-1/XBP-1 pathway, is activated by cold.
• Activation of this UPR pathway is linked to cold-induced endoplasmic reticulum stress.
• UPR activation through IRE-1/XBP-1 signaling enhances cold survival.

Conclusions:

• Cold adaptation in *C. elegans* relies on transcriptional regulation rather than global translation shutdown.
• The unfolded protein response (UPR) acts as a critical cold-survival mechanism.
• Cold-induced ER stress triggers the IRE-1/XBP-1 pathway, promoting cellular resilience.
• This study reveals a novel role for UPR in cold adaptation and survival.