Abstract
The conserved TREX-2 transcription-export complex integrates transcription and processing of many actively transcribed nascent mRNAs with the recruitment of export factors at nuclear pores and also contributes to transcriptional memory and genomic stability. We report the crystal structure of the Sac3-Thp1-Sem1 segment of Saccharomyces cerevisiae TREX-2 that interfaces with the gene expression machinery. Sac3-Thp1-Sem1 forms a previously uncharacterized PCI-domain complex characterized by the juxtaposition of Sac3 and Thp1 winged helix domains, forming a platform that mediates nucleic acid binding. Our structure-guided mutations support the idea that the Thp1-Sac3 interaction is an essential requirement for mRNA binding and for the coupling of transcription and processing to mRNP assembly and export. These results provide insight into how newly synthesized transcripts are efficiently transferred from TREX-2 to the principal mRNA export factor, and they reveal how Sem1 stabilizes PCI domain-containing proteins and promotes complex assembly.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Calcium-Binding Proteins / chemistry*
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism
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Cell Cycle Proteins / chemistry*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Conserved Sequence
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Humans
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Models, Molecular
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Molecular Sequence Data
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Nucleic Acids / metabolism*
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Nucleocytoplasmic Transport Proteins / chemistry
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Nucleocytoplasmic Transport Proteins / genetics
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Nucleocytoplasmic Transport Proteins / metabolism
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Porins / chemistry
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Porins / genetics
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Porins / metabolism
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Proteasome Endopeptidase Complex / chemistry
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Proteasome Endopeptidase Complex / genetics
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Proteasome Endopeptidase Complex / metabolism
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Protein Binding
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Protein Stability
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Protein Structure, Quaternary
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Protein Structure, Tertiary
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RNA Transport*
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RNA, Fungal / metabolism
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RNA, Messenger / metabolism
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RNA-Binding Proteins / chemistry
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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Ribonucleoproteins / chemistry
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Ribonucleoproteins / genetics
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Ribonucleoproteins / metabolism
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Saccharomyces cerevisiae / chemistry*
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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, Genetic*
Substances
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CDC31 protein, S cerevisiae
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Calcium-Binding Proteins
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Cell Cycle Proteins
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Nuclear Proteins
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Nucleic Acids
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Nucleocytoplasmic Transport Proteins
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Porins
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RNA, Fungal
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RNA, Messenger
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RNA-Binding Proteins
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Ribonucleoproteins
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SAC3 protein, S cerevisiae
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SEM1 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Sus1 protein, S cerevisiae
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Thp1 protein, S cerevisiae
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Proteasome Endopeptidase Complex