Crucial role of leaky initiation of uORF3 in the downregulation of HNT1 by ER stress.

eIF2α phosphorylation-mediated translational regulation is crucial for global repression of translation by various stresses, including the unfolded protein response (UPR) in eukaryotes. Although translational control during UPR has not been extensively investigated in S. cerevisiae, Hac1-mediated production of long transcripts containing uORFs was shown to repress the translation of histidine triad nucleotide-binding 1 (HNT1) mRNA.

The Ccr4-Not complex monitors the translating ribosome for codon optimality.

Control of messenger RNA (mRNA) decay rate is intimately connected to translation elongation, but the spatial coordination of these events is poorly understood. The Ccr4-Not complex initiates mRNA decay through deadenylation and activation of decapping. We used a combination of cryo-electron microscopy, ribosome profiling, and mRNA stability assays to examine the recruitment of Ccr4-Not to the ribosome via specific interaction of the Not5 subunit with the ribosomal E-site in This interaction occurred when the ribosome lacked accommodated A-site transfer RNA, indicative of low codon optimality.

Crucial role of ATP-bound Sse1 in Upf1-dependent degradation of the truncated product.

Up-frameshift (Upf) complex facilitates the degradation of aberrant mRNAs containing a premature termination codon (PTC) and its products in yeast. Here we report that Sse1, a member of the Hsp110 family, and Hsp70 play a crucial role in Upf-dependent degradation of the truncated FLAG-Pgk1-300 protein derived from PGK1 mRNA harboring a PTC at codon position 300. Sse1 was required for Upf-dependent rapid degradation of the FLAG-Pgk1-300.