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PMID:22767893
| Citation |
Padmanabhan, K, Robles, MS, Westerling, T and Weitz, CJ (2012) Feedback regulation of transcriptional termination by the mammalian circadian clock PERIOD complex. Science 337:599-602 |
|---|---|
| Abstract |
Eukaryotic circadian clocks are built on transcriptional feedback loops. In mammals, the PERIOD (PER) and CRYPTOCHROME (CRY) proteins accumulate, form a large nuclear complex (PER complex), and repress their own transcription. We found that mouse PER complexes included RNA helicases DDX5 and DHX9, active RNA polymerase II large subunit, Per and Cry pre-mRNAs, and SETX, a helicase that promotes transcriptional termination. During circadian negative feedback, RNA polymerase II accumulated near termination sites on Per and Cry genes but not on control genes. Recruitment of PER complexes to the elongating polymerase at Per and Cry termination sites inhibited SETX action, impeding RNA polymerase II release and thereby repressing transcriptional reinitiation. Circadian clock negative feedback thus includes direct control of transcriptional termination. |
| Links |
PubMed Online version:10.1126/science.1221592 |
| Keywords |
Animals; Circadian Clocks/genetics; Cryptochromes/genetics; Cryptochromes/metabolism; DEAD-box RNA Helicases/genetics; DEAD-box RNA Helicases/metabolism; Feedback, Physiological; Gene Expression Regulation; Mice; Period Circadian Proteins/genetics; Period Circadian Proteins/metabolism; RNA Polymerase II/genetics; RNA Polymerase II/metabolism; Transcription, Genetic |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
|
MOUSE:SETX |
involved_in |
GO:0007623: circadian rhythm |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
MOUSE:SETX |
involved_in |
GO:0006369: termination of RNA polymerase II transcription |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
MOUSE:SETX |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:O54943 |
F |
Seeded From UniProt |
complete | |
|
MOUSE:SETX |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:Q9DBR1 |
F |
Seeded From UniProt |
complete | |
|
MOUSE:PER2 |
involved_in |
GO:0060567: negative regulation of DNA-templated transcription, termination |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
MOUSE:PER2 |
enables |
GO:0036002: pre-mRNA binding |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | ||
|
MOUSE:PER2 |
enables |
GO:0070063: RNA polymerase binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:P08775 |
F |
Seeded From UniProt |
complete | |
|
MOUSE:PER2 |
located_in |
GO:0005634: nucleus |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
MOUSE:PER2 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:A2AKX3 |
F |
Seeded From UniProt |
complete | |
|
MOUSE:PER2 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:O70133 |
F |
Seeded From UniProt |
complete | |
|
MOUSE:PER2 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:Q3UYV9 |
F |
Seeded From UniProt |
complete | |
|
MOUSE:PER2 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:Q61656 |
F |
Seeded From UniProt |
complete | |
|
MOUSE:DHX9 |
involved_in |
GO:0007623: circadian rhythm |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | ||
|
MOUSE:DHX9 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:O54943 |
F |
Seeded From UniProt |
complete | |
|
MOUSE:DHX9 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:Q61656 |
F |
Seeded From UniProt |
complete | |
|
MOUSE:RPB1 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:O54943 |
F |
Seeded From UniProt |
complete | |
|
MOUSE:NCBP1 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:O54943 |
F |
Seeded From UniProt |
complete | |
|
involved_in |
GO:0007623: circadian rhythm |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:O54943 |
F |
Seeded From UniProt |
complete | ||
|
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:O70133 |
F |
Seeded From UniProt |
complete | ||
|
MOUSE:CDK9 |
located_in |
GO:0005634: nucleus |
ECO:0000314: direct assay evidence used in manual assertion |
C |
Seeded From UniProt |
complete | ||
|
MOUSE:CDK9 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:O54943 |
F |
Seeded From UniProt |
complete | |
|
MOUSE:XRN2 |
enables |
GO:0005515: protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
PR:A2AKX3 |
F |
Seeded From UniProt |
complete | |
|
acts_upstream_of_or_within |
GO:0007623: circadian rhythm |
ECO:0000315: mutant phenotype evidence used in manual assertion |
P |
occurs_in:(CL:0000057) |
Seeded From UniProt |
complete | ||
See also
References
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