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PMID:22767893

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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

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

MOUSE:DDX5

involved_in

GO:0007623: circadian rhythm

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:DDX5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:O54943

F

Seeded From UniProt

complete

MOUSE:DDX5

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

MOUSE:DDX5

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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