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

Area of Science:

• Molecular Biology
• Cell Biology
• Genetics

Background:

• Stress-induced messenger ribonucleoprotein (mRNP) condensation forms stress granules, but mRNA composition and function are unclear.
• Current understanding suggests mRNA sequence-dependent interactions cause condensation, favoring longer mRNAs.

Purpose of the Study:

• To investigate mRNA condensation and stress granule formation in budding yeast under various stresses.
• To identify factors determining mRNA inclusion or exclusion from stress-induced condensates.

Main Methods:

• Utilized budding yeast as a model organism.
• Applied multiple stress conditions.
• Analyzed mRNA condensation patterns and stress granule formation.
• Investigated translation initiation inhibition and its effect on mRNP condensates.

Main Results:

• Virtually all mRNAs condensed under stress with minimal length dependence, often without forming stress granules.
• Newly synthesized transcripts escaped mRNP condensation, enabling selective translation.
• Inhibiting translation initiation formed distinct mRNP condensates (TIICs) present even in unstressed cells.
• Stress-induced mRNAs were excluded from TIICs due to expression timing, not sequence.

Conclusions:

• mRNP condensation is a widespread stress response in yeast, not solely dependent on mRNA length or sequence.
• A novel layer of translation-linked molecular organization exists, with TIICs playing a role in stress response.
• The timing of mRNA expression is a key determinant for escaping mRNP condensation.