RNA as a crowding agent

Area of Science:

• Biochemistry and Molecular Biology
• Cell Biology
• Biophysics

Background:

• The intracellular environment is crowded, affecting biochemical reactions.
• RNA is a versatile polymer that contributes to cellular crowding through physical and interaction-based mechanisms.
• RNA's role extends beyond inert crowding agents, acting as a specific scaffold for molecular interactions.

Purpose of the Study:

• To review how RNA influences the formation, composition, and material properties of biomolecular condensates.
• To highlight the molecular grammar (sequence, length, structure, modifications) encoded in RNA that dictates condensate behavior.
• To discuss the biphasic effects of RNA concentration on condensate assembly and its implications for cellular function and disease.

Main Methods:

• Literature review and synthesis of existing research on RNA and biomolecular condensates.
• Analysis of RNA's physical contributions (diffusion restriction, excluded volume) and interaction-driven contributions (RNA-RNA, RNA-protein).
• Examination of structure-property relationships in RNA-mediated condensate formation.

Main Results:

• RNA actively shapes biomolecular condensates through sequence, structure, and valency.
• Concentration-dependent, biphasic effects of RNA on condensate assembly are observed.
• Aberrant RNA-mediated crowding is linked to neurodegenerative diseases and cancer.

Conclusions:

• RNA is a critical determinant of intracellular organization and biomolecular condensate properties.
• The molecular grammar of RNA dictates its role in functional compartmentalization versus pathological transitions.
• Challenges remain in defining RNA-specific thresholds and developing therapeutic strategies for RNA-mediated crowding.