About event
Cellular responses to environmental stress are regulated at both the transcriptional and posttranscriptional levels. Transcriptional regulation is efficient but relatively slow, and usually mediates long-term adaptation. By contrast, posttranscriptional regulation via RBPs allows gene expression to be rapidly altered in response to unfavorable environmental conditions. We previously developed the total RNA-associated proteome purification (TRAPP) protocol to isolate RBPs crosslinked to RNA. More recently, we used TRAPP to monitor global RBP dynamics in Saccharomyces cerevisiae in response to two well-characterized stress conditions: glucose starvation and heat shock. Each stress induced substantial remodeling of the RNA-protein interactome. Among the most notable changes, several ATP-dependent translation initiation factors involved in 40S scanning (eIF4A, eIF4B, and Ded1) lose binding to mRNAs entirely within just 30 seconds following glucose withdrawal. In parallel, already-initiated ribosomes finish elongating, allowing global translation to come to a halt in an orderly manner. These starkly different responses appear to be driven by rapid changes in the relative concentrations of intracellular ATP (powering translation initiation) and GTP (powering elongation) following glucose withdrawal.
Separately, our RNA-protein interactome screen identified several largely-uncharacterized RBPs. Among these were the related proteins Mrn1 and Nab6. We found that both proteins target a narrow and mostly overlapping set of cell wall-related mRNAs. Our results suggest that Nab6 acts in parallel to conventional transcriptional regulation pathways to maintain adequate expression of cell wall mRNAs during stress. Notably, Nab6-deficient cells are hypersensitive to antifungal compounds targeting the cell wall, highlighting the importance of posttranscriptional regulation in response to cell wall stress.
