Block of HAC1 mRNA translation by long-range base pairing is released by cytoplasmic splicing upon induction of the unfolded protein response.
Expression of the yeast transcription factor Hac1p, which controls the unfolded protein response, is regulated posttranscriptionally. Hac1p is only produced when an intron at the 3' end of its mRNA is removed by a nonconventional, regulated splicing reaction. We show that a previously unrecognized base-pairing interaction between the intron and the 5' untranslated region is required and sufficient to block mRNA translation. Unspliced HAC1 mRNA is stable, located in the cytosol, and is associated with polyribosomes, yet does not produce protein, indicating that the ribosomes engaged on the mRNA are stalled. We show that the polysomal, cytoplasmic pool of HAC1 mRNA is a substrate for splicing, suggesting that the stalled ribosomes may resume translation after the intron is removed.
Rüegsegger
U
U
Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.
Leber
J H
JH
Walter
P
P
D020121:5' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D017930:Genes, Reporter; D007438:Introns; D009690:Nucleic Acid Conformation; D014176:Protein Biosynthesis; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015003:Yeasts / Q000235:genetics / Q000378:metabolism
D020121:5' Untranslated Regions; D050976:Basic-Leucine Zipper Transcription Factors; D005656:Fungal Proteins; C091341:HAC1 protein, S cerevisiae; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors