Transcriptome-wide mRNP condensation precedes stress granule formation and excludes new mRNAs

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Stress granules are conserved cytoplasmic foci formed by mRNA and protein condensation during cellular stress.
• Previous models suggested stress-induced mRNA condensation results from ribosome-free RNA exposure and RNA length-dependent interactions.
• The precise mechanisms and functional relevance of stress granule formation, especially concerning transcriptional responses, remain incompletely understood.

Purpose of the Study:

• To investigate the mechanisms and characteristics of mRNA condensation in response to cellular stress.
• To determine the role of RNA features and translation status in stress-induced mRNA condensation.
• To elucidate how cells regulate translation of specific transcripts during stress conditions.

Main Methods:

• Utilized budding yeast as a model organism for studying stress responses.
• Employed endogenous genes and reporter constructs to track mRNA condensation.
• Applied biochemical detection methods to identify translation initiation-inhibited condensates (TIICs) and microscopy to visualize stress granules.

Main Results:

• Contrary to expectations, nearly all mRNA species condense during various stresses, with RNA length playing a minimal role.
• Condensation is triggered by translation initiation blockade, not solely by ribosome-free RNA.
• Stress-induced transcripts are preferentially excluded from condensates, facilitating their selective translation.
• Translation initiation-inhibited condensates (TIICs) are detectable biochemically and precede visible stress granule formation.
• Exclusion of stress-induced transcripts is primarily due to their expression timing, not sequence-specific features.

Conclusions:

• Stress-induced mRNA condensation is primarily driven by translation initiation inhibition, forming translation initiation-inhibited condensates (TIICs).
• Cells utilize TIICs to selectively translate newly synthesized stress-responsive transcripts by excluding them from the condensate.
• This mechanism allows for efficient cellular adaptation to changing environmental conditions by prioritizing essential gene expression during stress.