Figure 7.

Model of DRN mediated regulation of UPR activity in Saccharomyces cerevisiae. Precursor HAC1 mRNA with 3′-BE element is subjected to kinetic and preferential decay activity by DRN from 3′ to 5′ direction. In the absence of ER stress the precursor HAC1 mRNA undergoes an accelerated decay from 3′ to 5′ direction in a kinetic manner thus producing a higher population of precursor transcripts lacking the 3′-BE element resulting in a less efficient recruitment to Ire1p foci. Note that the degradation machinery does not stop after degrading the 3′-BE element, but continues to degrade the transcript body progressively in the 3′-5′ direction. This progressive degradation produces a heterogeneous population of pre-HAC1 transcripts having a heterogeneity at their 3′-termini most of which lack the 3′-BE. The absence of 3′-BE in these pre-HAC1 population would lead to reduced splicing by Ire1p/Rlg1p thereby resulting in the accumulation of precursor HAC1 transcript in the absence of ER stress. When ER stress is induced, degradation activity of DRN is diminished, which consequently generates a much higher population of precursor HAC1 mRNA population, most of which carry the functional BE element and is thereby targeted and recruited more efficiently to Ire1p foci. Increased recruitment of HAC1 precursor to Ire1p cluster results in increased splicing by Ire1p/Rlg1p thereby producing mature HAC1 mRNA and Hac1p for successful and efficient induction of UPR activity.