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Restrictor synergizes with Symplekin and PNUTS to terminate extragenic transcription

ABSTRACT: Transcription termination pathways mitigate the detrimental consequences of unscheduled promiscuous initiation occurring at hundreds of thousands of genomic cis-regulatory elements, thus representing cornerstones of genomic regulation in eukaryotes. Restrictor, a complex conserved from worms to humans and composed of the RNA-binding protein ZC3H4 and of WDR82, a Pol II-carboxyterminal repeat domain (CTD)-interacting protein, is required to suppress long-range, processive transcription at thousands of extragenic sites, with instead comparatively limited effects on gene transcription. Restrictor contains no RNA cleavage subunit and does not coopt known cleavage complexes, indicating alternative termination mechanisms. Here we show that Restrictor-driven termination involves Symplekin, a protein associated with RNA cleavage complexes but also involved in cleavage-independent, phosphatase-dependent termination of non-coding RNAs in yeast. Competition among Restrictor, the cleavage and polyadenylation specificity complex (CPSF) and the histone cleavage complex for a limited pool of Symplekin resulted in mutual regulation, thus revealing unexpected regulatory interactions among multiple transcription termination pathways and a general role of Symplekin in both genic and extragenic cleavage-independent termination pathways.

ORGANISM(S): Homo sapiens

PROVIDER: GSE237459 | GEO | 2023/12/14

REPOSITORIES: GEO

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Restrictor synergizes with Symplekin and PNUTS to terminate extragenic transcription

Project description:Transcription termination pathways mitigate the detrimental consequences of unscheduled promiscuous initiation occurring at hundreds of thousands of genomic cis-regulatory elements. The Restrictor complex, composed of the Pol II-interacting protein WDR82 and the RNA-binding protein ZC3H4, suppresses processive transcription at thousands of extragenic sites in mammalian genomes. Restrictor-driven termination does not involve nascent RNA cleavage and its interplay with other termination machineries is unclear. Here we show that efficient termination at Restrictor-controlled extragenic transcription units involves the recruitment of the protein phosphatase 1 (PP1) regulatory subunit PNUTS, a negative regulator of the Spt5 elongation factor, and Symplekin, a protein associated with RNA cleavage complexes but also involved in cleavage-independent and phosphatase-dependent termination of non-coding RNAs in yeast. PNUTS and Symplekin act synergistically with, but independently from Restrictor to dampen processive extragenic transcription. Moreover, the presence of limiting nuclear levels of Symplekin imposes a competition for its recruitment among multiple transcription termination machineries, resulting in mutual regulatory interactions. Hence, by synergizing with Restrictor, Symplekin and PNUTS enable efficient termination of processive, long-range extragenic transcription.

2024-05-23 | PXD043638 | Pride

Restrictor synergizes with Symplekin and PNUTS to terminate extragenic transcription

Project description:Transcription termination pathways mitigate the detrimental consequences of unscheduled promiscuous initiation occurring at hundreds of thousands of genomic cis-regulatory elements, thus representing cornerstones of genomic regulation in eukaryotes. Restrictor, a complex conserved from worms to humans and composed of the RNA-binding protein ZC3H4 and of WDR82, a Pol II-carboxyterminal repeat domain (CTD)-interacting protein, is required to suppress long-range, processive transcription at thousands of extragenic sites, with instead comparatively limited effects on gene transcription. Restrictor contains no RNA cleavage subunit and does not coopt known cleavage complexes, indicating alternative termination mechanisms. Here we show that Restrictor-driven termination involves Symplekin, a protein associated with RNA cleavage complexes but also involved in cleavage-independent, phosphatase-dependent termination of non-coding RNAs in yeast. Competition among Restrictor, the cleavage and polyadenylation specificity complex (CPSF) and the histone cleavage complex for a limited pool of Symplekin resulted in mutual regulation, thus revealing unexpected regulatory interactions among multiple transcription termination pathways and a general role of Symplekin in both genic and extragenic cleavage-independent termination pathways.

2023-12-14 | GSE240357 | GEO

Restrictor synergizes with Symplekin and PNUTS to terminate extragenic transcription

Project description:Transcription termination pathways mitigate the detrimental consequences of unscheduled promiscuous initiation occurring at hundreds of thousands of genomic cis-regulatory elements, thus representing cornerstones of genomic regulation in eukaryotes. Restrictor, a complex conserved from worms to humans and composed of the RNA-binding protein ZC3H4 and of WDR82, a Pol II-carboxyterminal repeat domain (CTD)-interacting protein, is required to suppress long-range, processive transcription at thousands of extragenic sites, with instead comparatively limited effects on gene transcription. Restrictor contains no RNA cleavage subunit and does not coopt known cleavage complexes, indicating alternative termination mechanisms. Here we show that Restrictor-driven termination involves Symplekin, a protein associated with RNA cleavage complexes but also involved in cleavage-independent, phosphatase-dependent termination of non-coding RNAs in yeast. Competition among Restrictor, the cleavage and polyadenylation specificity complex (CPSF) and the histone cleavage complex for a limited pool of Symplekin resulted in mutual regulation, thus revealing unexpected regulatory interactions among multiple transcription termination pathways and a general role of Symplekin in both genic and extragenic cleavage-independent termination pathways.

2023-12-14 | GSE237458 | GEO

Restrictor synergizes with Symplekin and PNUTS to terminate extragenic transcription

Project description:Transcription termination pathways mitigate the detrimental consequences of unscheduled promiscuous initiation occurring at hundreds of thousands of genomic cis-regulatory elements, thus representing cornerstones of genomic regulation in eukaryotes. Restrictor, a complex conserved from worms to humans and composed of the RNA-binding protein ZC3H4 and of WDR82, a Pol II-carboxyterminal repeat domain (CTD)-interacting protein, is required to suppress long-range, processive transcription at thousands of extragenic sites, with instead comparatively limited effects on gene transcription. Restrictor contains no RNA cleavage subunit and does not coopt known cleavage complexes, indicating alternative termination mechanisms. Here we show that Restrictor-driven termination involves Symplekin, a protein associated with RNA cleavage complexes but also involved in cleavage-independent, phosphatase-dependent termination of non-coding RNAs in yeast. Competition among Restrictor, the cleavage and polyadenylation specificity complex (CPSF) and the histone cleavage complex for a limited pool of Symplekin resulted in mutual regulation, thus revealing unexpected regulatory interactions among multiple transcription termination pathways and a general role of Symplekin in both genic and extragenic cleavage-independent termination pathways.

2023-12-14 | GSE237457 | GEO