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The USP11/TCEAL1 complex promotes transcription elongation to sustain oncogenic gene expression in neuroblastoma [RNA-seq II]

ABSTRACT: During early transcription, RNA polymerase II (RNAPII) undergoes a series of structural transitions controlled by cyclin-dependent kinases. How protein ubiquitylation and proteasomal degradation control the function of RNAPII is less well understood. Here we show that the deubiquitinating enzyme USP11 forms a complex with TCEAL1, a member of the TFIIS (TCEA)-like protein family. TCEAL1 shares sequence homology with the RNAPII interaction domain of the elongation factor TFIIS, which controls the fate of backtracked RNAPII, and competes with TFIIS for binding to core promoters, potentially preventing excessive backtracking. USP11 protects TCEAL1 from proteasomal degradation and TCEAL1 recruits USP11 to RNAPII. Both USP11 and TCEAL1 promote transcription elongation and maintain expression of RPB8, an essential subunit of all three nuclear RNA polymerases. In neuroblastoma USP11- and TCEAL1-dependent genes define a gene expression program that is characteristic for mesenchymal tumors, which are described to escape from many treatments, suggesting that the USP11/TCEAL1 complex promotes transcription elongation to support a critical oncogenic gene expression program

ORGANISM(S): Homo sapiens

PROVIDER: GSE294526 | GEO | 2025/04/25

REPOSITORIES: GEO

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The USP11/TCEAL1 complex promotes transcription elongation to sustain oncogenic gene expression in neuroblastoma [ChIP-seq II]

Project description:During early transcription, RNA polymerase II (RNAPII) undergoes a series of structural transitions controlled by cyclin-dependent kinases. How protein ubiquitylation and proteasomal degradation control the function of RNAPII is less well understood. Here we show that the deubiquitinating enzyme USP11 forms a complex with TCEAL1, a member of the TFIIS (TCEA)-like protein family. TCEAL1 shares sequence homology with the RNAPII interaction domain of the elongation factor TFIIS, which controls the fate of backtracked RNAPII, and competes with TFIIS for binding to core promoters, potentially preventing excessive backtracking. USP11 protects TCEAL1 from proteasomal degradation and TCEAL1 recruits USP11 to RNAPII. Both USP11 and TCEAL1 promote transcription elongation and maintain expression of RPB8, an essential subunit of all three nuclear RNA polymerases. In neuroblastoma USP11- and TCEAL1-dependent genes define a gene expression program that is characteristic for mesenchymal tumors, which are described to escape from many treatments, suggesting that the USP11/TCEAL1 complex promotes transcription elongation to support a critical oncogenic gene expression program

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A trimeric USP11-USP7-TCEAL1 complex stabilizes paused RNAPII to sustain oncogenic transcription

Project description:A trimeric USP11-USP7-TCEAL1 complex stabilizes paused RNAPII to sustain oncogenic transcription

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A trimeric USP11-USP7-TCEAL1 complex stabilizes paused RNAPII to sustain oncogenic transcription [RNA-seq]

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