Glauninger, H. | bioRxiv Science

bioRxiv2024

Transcriptome-wide mRNA condensation precedes stress granule formation and excludes stress-induced transcripts

Stress-induced mRNP condensation is conserved across eukaryotes, resulting in stress granule formation under intense stresses, yet the mRNA composition and function of these condensates remain unclear. Exposure of ribosome-free mRNA following stress is thought to cause condensation and stress granule formation through mRNA-sequence-dependent interactions, leading to disproportionate condensation of long mRNAs. Here we show that, in striking contrast, virtually all mRNAs condense in response to multiple stresses in budding yeast with minor length dependence and often without stress granule formation. New transcripts escape mRNP condensation, enabling their selective translation. Inhibiting translation initiation causes formation of mRNP condensates that are distinct from stress granules and P-bodies; these translation-initiation-inhibited condensates (TIICs) are omnipresent, even in unstressed cells. Stress-induced mRNAs are excluded from TIICs due to the timing of their expression, indicating determinants of escape that are independent of sequence. Together, our results reveal a previously undetected level of translation-linked molecular organization and stress-responsive regulation.

cell biology↗

bioRxiv2023

An adaptive biomolecular condensation response is conserved across environmentally divergent species

Cells must sense and respond to sudden maladaptive environmental changes--stresses--to survive and thrive. Across eukaryotes, stresses such as heat shock trigger conserved responses: growth arrest, a specific transcriptional response, and biomolecular condensation of protein and mRNA into structures known as stress granules under severe stress. The composition, formation mechanism, adaptive significance, and even evolutionary conservation of these condensed structures remain enigmatic. Here we provide an unprecedented view into stress-triggered condensation, its evolutionary conservation and tuning, and its integration into other well-studied aspects of the stress response. Using three morphologically near-identical budding yeast species adapted to different thermal environments and diverged by up to 100 million years, we show that proteome-scale biomolecular condensation is tuned to species-specific thermal niches, closely tracking corresponding growth and transcriptional responses. In each species, poly(A)-binding protein--a core marker of stress granules--condenses in isolation at species-specific temperatures, with conserved molecular features and conformational changes modulating condensation. From the ecological to the molecular scale, our results reveal previously unappreciated levels of evolutionary selection in the eukaryotic stress response, while establishing a rich, tractable system for further inquiry.

cell biology↗