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PMID: 9927427 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

TIMELESS-dependent positive and negative autoregulation in the Drosophila circadian clock.

The EMBO journal ·Vol. 18 ·No. 3 ·1999-02-01 ·Pages 675-86

Suri V, Lanjuin A, Rosbash M

Abstract

The timeless protein (TIM) is a central component of the circadian pacemaker machinery of the fruitfly Drosophila melanogaster. Both TIM and its partner protein, the period protein PER, show robust circadian oscillations in mRNA and protein levels. Yet the role of TIM in the rhythm generation mechanism is largely unknown. To analyze TIM function, we constructed transgenic flies that carry a heat shock-inducible copy of the timeless gene (tim) in an arrhythmic tim loss-of-function genetic background. When heat shocked, TIM levels in these flies rapidly increased and initiated a molecular cycle of PER accumulation and processing with dynamics very similar to the PER cycle observed in wild-type flies. Analysis of period (per) mRNA levels and transcription uncovered a novel role for TIM in clock regulation: TIM increases per mRNA levels through a post-transcriptional mechanism. Our results suggest positive as well as negative autoregulation in the Drosophila circadian clock.

MeSH Terms
ARNTL Transcription Factors Animals Animals, Genetically Modified Basic Helix-Loop-Helix Transcription Factors Circadian Rhythm/genetics,physiology Dimerization Drosophila Proteins Drosophila melanogaster/genetics,physiology Gene Expression Genes, Insect Homeostasis Hot Temperature Insect Proteins/chemistry,genetics,physiology Models, Biological Nuclear Proteins/chemistry,genetics,physiology Period Circadian Proteins Phosphorylation Protein Conformation RNA Processing, Post-Transcriptional RNA, Messenger/genetics,metabolism Trans-Activators/genetics,physiology Transcription, Genetic
Chemicals
ARNTL Transcription Factors Basic Helix-Loop-Helix Transcription Factors Drosophila Proteins Insect Proteins Nuclear Proteins PER protein, Drosophila Period Circadian Proteins RNA, Messenger Trans-Activators cyc protein, Drosophila tim protein, Drosophila
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Suri V
Department of Biochemistry, Howard Hughes Medical Institute, 415 South Street, Brandeis University, Waltham, MA 02454, USA.
Lanjuin A
Rosbash M
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/18.3.675
Published
1999-02-01
Pages
675-86
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1171160
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/18.3.675 PMC Full Text View journal details
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