Stress-granules, P-bodies, and cell aging: A bioinformatics study

Area of Science:

• Cell Biology
• Biochemistry
• Aging Research

Background:

• Aging is linked to the dysfunction and altered material properties of stress-induced membrane-less organelles (MLOs).
• Stress granules (SGs) and P-bodies are key MLOs involved in cellular stress responses.
• Understanding the proteomic changes within MLOs during aging is crucial for deciphering cellular senescence.

Purpose of the Study:

• To analyze the proteomes of SGs and P-bodies for proteins influencing MLO physical state, especially those with altered expression during aging.
• To investigate the role of intrinsically disordered proteins and liquid-liquid phase separation (LLPS) in MLOs during cellular senescence.
• To identify specific protein characteristics and interactions within MLOs associated with aging.

Main Methods:

• Proteomic analysis of SGs and P-bodies.
• Bioinformatic analysis of protein properties, including charge, binding capabilities (DNA/RNA), and amyloidogenic potential.
• Identification of protein-protein interaction networks for senescence-associated proteins within MLOs.

Main Results:

• MLOs are enriched in intrinsically disordered proteins, with 30-40% capable of liquid-liquid phase separation (LLPS).
• Proteins with altered gene expression during senescence constitute ~20% of the studied MLO proteomes, showing increased positive charge.
• SG proteins, particularly those involved in senescence, exhibit increased DNA-binding and amyloidogenic potential compared to P-body proteins.

Conclusions:

• SG proteins are more likely than P-body proteins to alter the physical state of MLOs during aging.
• MLOs, particularly SGs, play a significant role in cellular senescence through coordinated protein interactions and altered material properties.
• These findings highlight the dynamic nature of MLOs in aging and senescence.