Dual functions of yeast tRNA ligase in the unfolded protein response: unconventional cytoplasmic splicing of HAC1 pre-mRNA is not sufficient to release translational attenuation

Mol Biol Cell. 2010 Nov 1;21(21):3722-34. doi: 10.1091/mbc.E10-08-0693. Epub 2010 Sep 15.


The unfolded protein response (UPR) is an essential signal transduction to cope with protein-folding stress in the endoplasmic reticulum. In the yeast UPR, the unconventional splicing of HAC1 mRNA is a key step. Translation of HAC1 pre-mRNA (HAC1(u) mRNA) is attenuated on polysomes and restarted only after splicing upon the UPR. However, the precise mechanism of this restart remained unclear. Here we show that yeast tRNA ligase (Rlg1p/Trl1p) acting on HAC1 ligation has an unexpected role in HAC1 translation. An RLG1 homologue from Arabidopsis thaliana (AtRLG1) substitutes for yeast RLG1 in tRNA splicing but not in the UPR. Surprisingly, AtRlg1p ligates HAC1 exons, but the spliced mRNA (HAC1(i) mRNA) is not translated efficiently. In the AtRLG1 cells, the HAC1 intron is circularized after splicing and remains associated on polysomes, impairing relief of the translational repression of HAC1(i) mRNA. Furthermore, the HAC1 5' UTR itself enables yeast Rlg1p to regulate translation of the following ORF. RNA IP revealed that yeast Rlg1p is integrated in HAC1 mRNP, before Ire1p cleaves HAC1(u) mRNA. These results indicate that the splicing and the release of translational attenuation of HAC1 mRNA are separable steps and that Rlg1p has pivotal roles in both of these steps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Basic-Leucine Zipper Transcription Factors / biosynthesis
  • Basic-Leucine Zipper Transcription Factors / genetics*
  • Cytoplasm / metabolism
  • Gene Expression Regulation, Fungal
  • Introns
  • Phosphoric Diester Hydrolases / genetics
  • Phosphoric Diester Hydrolases / metabolism*
  • Polynucleotide 5'-Hydroxyl-Kinase / genetics
  • Polynucleotide 5'-Hydroxyl-Kinase / metabolism*
  • Polynucleotide Ligases / genetics
  • Polynucleotide Ligases / metabolism*
  • RNA Precursors / genetics
  • RNA Precursors / metabolism*
  • RNA Splicing
  • Repressor Proteins / biosynthesis
  • Repressor Proteins / genetics*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / biosynthesis
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Unfolded Protein Response*


  • Basic-Leucine Zipper Transcription Factors
  • HAC1 protein, S cerevisiae
  • RNA Precursors
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • tRNA ligase, yeast
  • Polynucleotide 5'-Hydroxyl-Kinase
  • Phosphoric Diester Hydrolases
  • Polynucleotide Ligases