Abstract
During eukaryotic transcription elongation, RNA polymerase II (RNAP2) is regulated by a chorus of factors. Here, we identified a common binary interaction module consisting of TFIIS N-terminal domains (TNDs) and natively unstructured TND-interacting motifs (TIMs). This module was conserved among the elongation machinery and linked complexes including transcription factor TFIIS, Mediator, super elongation complex, elongin, IWS1, SPT6, PP1-PNUTS phosphatase, H3K36me3 readers, and other factors. Using nuclear magnetic resonance, live-cell microscopy, and mass spectrometry, we revealed the structural basis for these interactions and found that TND-TIM sequences were necessary and sufficient to induce strong and specific colocalization in the crowded nuclear environment. Disruption of a single TIM in IWS1 induced robust changes in gene expression and RNAP2 elongation dynamics, which underscores the functional importance of TND-TIM surfaces for transcription elongation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / chemistry
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Adaptor Proteins, Signal Transducing / metabolism
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Cell Line, Tumor
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DNA-Binding Proteins / chemistry
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DNA-Binding Proteins / metabolism
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Gene Expression
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Humans
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Intrinsically Disordered Proteins / chemistry*
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Intrinsically Disordered Proteins / metabolism
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Models, Molecular
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Mutation
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Protein Binding
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Protein Domains
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Protein Interaction Domains and Motifs / genetics
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Protein Interaction Maps
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RNA Polymerase II / chemistry
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RNA Polymerase II / 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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Transcription Elongation, Genetic*
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Transcription Factors / chemistry*
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcriptional Elongation Factors / chemistry*
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Transcriptional Elongation Factors / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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DNA-Binding Proteins
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Intrinsically Disordered Proteins
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Iws1 protein, human
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PPP1R10 protein, human
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PSIP1 protein, human
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RNA-Binding Proteins
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Transcription Factors
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Transcriptional Elongation Factors
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transcription factor S-II
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RNA Polymerase II