Figure 9.

Proposed model for inhibition of HAC1^u mRNA splicing by RTA. A, HAC1^u mRNA associates with ribosomes and begins to be translated as the 5′ end emerges from the nucleus. When the intron at the 3′-UTR enters the cytoplasm, it base-pairs with the 5′-UTR, thereby forming a closed loop that prevents translation initiation. Removal of the intron by IRE1 during ER stress allows translation of HAC1ⁱ. B, HAC1^u mRNA associates with the ribosome as it is exported from the nucleus. Translation begins, but ribosome depurination by RTA traps ribosomes on HAC1^u mRNA, preventing the base-pairing interaction between the 5′-UTR and the intron. The inability to form base pairing impedes the process by which HAC1^u can be spliced during ER stress.