A family of unusually spliced biologically active transcripts encoded by a Drosophila clock gene

Citri, Yoav; Colot, Hildur V.; Jacquier, Agnes C.; Yu, Qiang; Hall, Jeffrey C.; Baltimore, David; Rosbash, Michael

doi:10.1038/326042a0

Cited by 226 publications

(169 citation statements)

References 47 publications

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“…A potential role for SARs in the process of transcription is suggested by the observation that some SARs comap with limits of nuclease-sensitive domains (7,27,41) and that the presence of SARs next to transcription units tend to reduce position effects during transformation (11,21,23,35,46). On the other hand, certain data support the idea that SARs may be involved in the replication process.…”

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confidence: 99%

Studies of an 800-kilobase DNA stretch of the Drosophila X chromosome: comapping of a subclass of scaffold-attached regions with sequences able to replicate autonomously in Saccharomyces cerevisiae.

Brun¹,

Dang²,

Miassod³

1990

Mol. Cell. Biol.

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We have previously mapped scaffold-attached regions (SARs) on an 800-kilobase DNA walk from the Drosophila X chromosome. We have also previously shown that the strength of binding, i.e., the ability of SARs to bind to all nuclear scaffolds or only to a fraction of them varied from one SAR to another one. In the present study, 71 of the 85 subfragments that bind scaffolds and 38 fragments that do not bind scaffolds were tested for their ability to promote autonomous replicating sequence (ARS) activity in Saccharomyces cerevisiae. Sixteen SAR-containing fragments from the chromosome walk were also examined for association to yeast nuclear scaffolds in vitro. All identified ARSs (a total of 27) were present on SAR-containing fragments, except two, which were adjacent to SARs. There is thus a correlation between ARS and SAR activities, and this correlation defines a SAR subclass. Moreover, the presence of an ARS on a DNA fragment appeared to be highly correlated with the strength of binding. The binding activity was highly conserved from Drosophila melanogaster to yeast. These data suggest that Drosophila DNA sequences responsible for binding to components of the nuclear scaffold from either D. melanogaster or yeast may be involved in the process of heterologous extrachromosomal replication in yeasts.Electron microscopic and sedimentation analyses of histone-depleted chromosomes and nuclei (5, 14, 40, 52) support the hypothesis that eucaryotic DNA is organized as individual loops constrained at their bases by interaction of DNA with nonhistone proteins. Laemmli and co-workers (37) have proposed an extraction procedure in which lithium 3'-5'-diiodosalicylate (LIS) is used to isolate specific DNA fragments which presumably form the bases of the loops. This technique has been applied to various parts of the

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confidence: 99%

Studies of an 800-kilobase DNA stretch of the Drosophila X chromosome: comapping of a subclass of scaffold-attached regions with sequences able to replicate autonomously in Saccharomyces cerevisiae.

Brun¹,

Dang²,

Miassod³

1990

Mol. Cell. Biol.

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“…Locomotor activity was also affected, and each per mutation produced equivalent effects on eclosion and locomotor activity rhythms. More than a decade passed before the molecular identity of period was established (Bargiello and Young 1984;Reddy et al 1984;Jackson et al 1986;Citri et al 1987). Yet, the primary sequence of the encoded protein provided little information about its function in circadian rhythm generation.…”

Section: Introductionmentioning

confidence: 99%

A PER/TIM/DBT Interval Timer forDrosophila's Circadian Clock

Sáez¹,

Meyer²,

Young³

2007

Cold Spring Harbor Symposia on Quantitative Biology

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Circadian rhythms in Drosophila are supported by a negative feedback loop, in which PERIOD (PER) and Timeless (TIM) shut down their own transcription as they translocate once a day from the cytoplasm of clock-containing cells to the nucleus. Period length is partially determined by an interval of cytoplasmic retention of the TIM and PER proteins. To study this process, we examined PER/TIM/Doubletime (DBT) physical interactions and nuclear translocation by imaging individual cultured Drosophila cells. Using live cell video microscopy and green fluorescent protein (GFP) tags, we observed dynamic patterns of stability and localization for DBT, PER, and TIM that resembled those previously found in vivo. These studies suggest that a cytoplasmic interval timer regulates nuclear translocation of these proteins. The cultured cell assay provides a potent system to study interactions among new and known genes involved in the generation of circadian behavior.

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“…For example, the core clock genes period in Drosophila and frequency in Neurospora give rise to different mRNA isoforms through AS, which helps these organisms adjust to different temperature conditions (4,5,12). Four different BMAL2 transcripts, encoding proteins with varying levels of transcriptional activity, are generated by AS in humans; however, it remains to be determined whether these transcripts have different physiological functions (13).…”

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Role for LSM genes in the regulation of circadian rhythms

Perez-Santángelo

Mancini

Francey

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Growing evidence suggests that core spliceosomal components differentially affect RNA processing of specific genes; however, whether changes in the levels or activities of these factors control specific signaling pathways is largely unknown. Here we show that some SM-like (LSM) genes, which encode core components of the spliceosomal U6 small nuclear ribonucleoprotein complex, regulate circadian rhythms in plants and mammals. We found that the circadian clock regulates the expression of LSM5 in Arabidopsis plants and several LSM genes in mouse suprachiasmatic nucleus. Further, mutations in LSM5 or LSM4 in Arabidopsis, or down-regulation of LSM3, LSM5, or LSM7 expression in human cells, lengthens the circadian period. Although we identified changes in the expression and alternative splicing of some core clock genes in Arabidopsis lsm5 mutants, the precise molecular mechanism causing period lengthening remains to be identified. Genome-wide expression analysis of either a weak lsm5 or a strong lsm4 mutant allele in Arabidopsis revealed larger effects on alternative splicing than on constitutive splicing. Remarkably, large splicing defects were not observed in most of the introns evaluated using RNA-seq in the strong lsm4 mutant allele used in this study. These findings support the idea that some LSM genes play both regulatory and constitutive roles in RNA processing, contributing to the fine-tuning of specific signaling pathways.posttranscriptional | alternative splicing | circadian clock | Arabidopsis | mammals C ircadian rhythms are persistent 24-h oscillations in biological processes that occur under constant environmental conditions. They allow organisms to coordinate multiple physiological processes with periodic or seasonal changes that occur in the environment. At the heart of the eukaryotic circadian system lies a complex set of interconnected transcriptional and translational feedback loops, in which a group of core clock genes regulate each other to ensure that their mRNA levels oscillate with a period of ∼24 h (1). The core oscillator in Arabidopsis thaliana involves two MYB domain-containing transcription factors, CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and LATE ELONGATED HYPOCOTYL (LHY), that repress the expression of TIMING OF CAB2 EXPRESSION 1 (TOC1) at the beginning of the day. In turn, TOC1, a member of the PSEUDO-RESPONSE REGULATOR (PRR) family, represses CCA1/LHY expression at the end of the day (2). Other clock components expressed throughout the day form multiple interconnected transcriptional feedback loops (2).Mounting evidence indicates that alternative splicing (AS), the process by which pre-mRNA molecules are differentially spliced to yield multiple mRNA isoforms from a single gene, plays a key role in the regulation of circadian networks in a variety of organisms, including Drosophila melanogaster (3), Neurospora crassa (4-6), and Arabidopsis (7-11). For example, the core clock genes period in Drosophila and frequency in Neurospora give rise to different mRNA isoforms through AS, which helps t...

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A family of unusually spliced biologically active transcripts encoded by a Drosophila clock gene

Cited by 226 publications

References 47 publications

Studies of an 800-kilobase DNA stretch of the Drosophila X chromosome: comapping of a subclass of scaffold-attached regions with sequences able to replicate autonomously in Saccharomyces cerevisiae.

Studies of an 800-kilobase DNA stretch of the Drosophila X chromosome: comapping of a subclass of scaffold-attached regions with sequences able to replicate autonomously in Saccharomyces cerevisiae.

A PER/TIM/DBT Interval Timer forDrosophila's Circadian Clock

Role for LSM genes in the regulation of circadian rhythms

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