ArticlePLoS genetics2015
Drosophila TIM binds importin α1, and acts as an adapter to transport PER to the nucleus.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 67 citations in OpenAlex.
- Rhythmic nuclear import mediated by importins regulates the Neurospora circadian clock.Genetics · 2026Article
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Rhythmic Nuclear Import Mediated by Importins Regulates thebioRxiv : the preprint server for biology · 2026Article
- Coevolution ofiScience · 2025Article
- Article
- Circadian rhythms in the Drosophila eye may regulate adaptation of vision to light intensity.Frontiers in neuroscience · 2024Article
- A novel method for identifying key genes in macroevolution based on deep learning with attention mechanism.Scientific reports · 2023Article
- CLOCK and TIMELESS regulate rhythmic occupancy of the BRAHMA chromatin-remodeling protein at clock gene promoters.PLoS genetics · 2023Article
- Spatial and temporal control of expression with light-gated LOV-LexA.G3 (Bethesda, Md.) · 2022Article
- Evolution of casein kinase 1 and functional analysis of newFrontiers in physiology · 2022Article
- Activation of the clock gene TIMELESS by H3k27 acetylation promotes colorectal cancer tumorigenesis by binding to Myosin-9.Journal of experimental & clinical cancer research : CR · 2021Article
- CK2 Inhibits TIMELESS Nuclear Export and Modulates CLOCK Transcriptional Activity to Regulate Circadian Rhythms.Current biology : CB · 2021Article
- Regulation of Plant Immunity by Nuclear Membrane-Associated Mechanisms.Frontiers in immunology · 2021Review
- TIMELESS Promotes Tumor Progression by Enhancing Macrophages Recruitment in Ovarian Cancer.Frontiers in oncology · 2021Article
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- Article
- Critical role of deadenylation in regulating poly(A) rhythms and circadian gene expression.PLoS computational biology · 2020Article
- Molecular mechanisms and physiological importance of circadian rhythms.Nature reviews. Molecular cell biology · 2020Review
- Circadian gene variants and the skeletal muscle circadian clock contribute to the evolutionary divergence in longevity acrossGenome research · 2019Article
- PERIOD-controlled deadenylation of theProceedings of the National Academy of Sciences of the United States of America · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Regulated nuclear entry of clock proteins is a conserved feature of eukaryotic circadian clocks and serves to separate the phase of mRNA activation from mRNA repression in the molecular feedback loop. In Drosophila, nuclear entry of the clock proteins, PERIOD (PER) and TIMELESS (TIM), is tightly controlled, and impairments of this process produce profound behavioral phenotypes. We report here that nuclear entry of PER-TIM in clock cells, and consequently behavioral rhythms, require a specific member of a classic nuclear import pathway, Importin α1 (IMPα1). In addition to IMPα1, rhythmic behavior and nuclear expression of PER-TIM require a specific nuclear pore protein, Nup153, and Ran-GTPase. IMPα1 can also drive rapid and efficient nuclear expression of TIM and PER in cultured cells, although the effect on PER is mediated by TIM. Mapping of interaction domains between IMPα1 and TIM/PER suggests that TIM is the primary cargo for the importin machinery. This is supported by attenuated interaction of IMPα1 with TIM carrying a mutation previously shown to prevent nuclear entry of TIM and PER. TIM is detected at the nuclear envelope, and computational modeling suggests that it contains HEAT-ARM repeats typically found in karyopherins, consistent with its role as a co-transporter for PER. These findings suggest that although PER is the major timekeeper of the clock, TIM is the primary target of nuclear import mechanisms. Thus, the circadian clock uses specific components of the importin pathway with a novel twist in that TIM serves a karyopherin-like role for PER.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.