Abstract
The unconventional splicing of Hac1 by the ribonuclease Ire1 is a key event in the activation of the unfolded protein response (UPR) in Saccharomyces cerevisiae. This splicing is independent of the spliceosome and is mediated by a secondary structure at the intron-exon boundaries of the mRNA. Similar unconventional splicing was also described for the gene Xbp1 in human, mouse, C. elegans and D. melanogaster, and for Hac1 in five other fungi. We used reported RNA structures to build a multiple sequence alignment and the Infernal package to search for homologous structures. We identified homologous non-canonical intron structures in 128 out of 156 searched eukaryotic genomes. Our results show that the sequence of the Hac1/Xbp1 intron is highly conserved only around the splice sites recognized by Ire1. The consensus structure of the Hac1/Xbp1 mRNA is well conserved in Fungi and Metazoa and resembles structures previously described. We show that a typical Hac1/Xbp1 intron is very short, only 20-26 bases, whereas yeast species have a long intron (> 100 bases). We identified six species with unambiguous Hac1/Xbp1 homologs that have lost the non-canonical intron structure. We propose that these species use a different mechanism to regulate the UPR.
MeSH terms
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Animals
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Basic-Leucine Zipper Transcription Factors / chemistry
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Basic-Leucine Zipper Transcription Factors / genetics*
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / genetics
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / genetics*
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Drosophila Proteins / chemistry
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Drosophila Proteins / genetics
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Fungal Proteins / chemistry
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Fungal Proteins / genetics
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Gene Expression Regulation, Fungal
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Humans
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Introns*
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics*
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Membrane Glycoproteins / metabolism
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Nucleic Acid Conformation
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Protein Folding
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / genetics*
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Protein Serine-Threonine Kinases / metabolism
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Protein Splicing
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RNA / chemistry*
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RNA / genetics
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RNA Splicing
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RNA, Fungal / chemistry*
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RNA, Fungal / genetics
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Regulatory Factor X Transcription Factors
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Repressor Proteins / chemistry
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Repressor Proteins / genetics*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / genetics*
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Saccharomyces cerevisiae Proteins / metabolism
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Sequence Alignment
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Transcription Factors / chemistry
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Transcription Factors / genetics*
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Unfolded Protein Response / genetics
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X-Box Binding Protein 1
Substances
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Basic-Leucine Zipper Transcription Factors
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Caenorhabditis elegans Proteins
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DNA-Binding Proteins
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Drosophila Proteins
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Fungal Proteins
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HAC1 protein, S cerevisiae
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Membrane Glycoproteins
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RNA, Fungal
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Regulatory Factor X Transcription Factors
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Repressor Proteins
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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X-Box Binding Protein 1
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XBP1 protein, S cerevisiae
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XBP1 protein, human
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Xbp1 protein, mouse
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RNA
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IRE1 protein, S cerevisiae
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Protein Serine-Threonine Kinases