The novel gene twenty-four defines a critical translational step in the Drosophila clock

Lim, Chunghun; Lee, Jong Bin; Choi, Changtaek; Kilman, Valerie L.; Kim, Juwon; Park, Sung Mi; Jang, Sung Key; Allada, Ravi; Choe, Joonho

doi:10.1038/nature09728

Cited by 78 publications

(117 citation statements)

References 51 publications

Supporting

Mentioning

107

Contrasting

Order By: Relevance

“…TIM signal was also reduced in PDF cells ( Figure 3C), indicating that tim mRNA may also be subject to atypical translation. This notion is consistent with the finding that mRNA for both genes binds to TYF (Lim et al 2011). Although TIM is required for PER stability (Price et al 1995), our rescue experiments in PDF cells indicate that PER is probably the NAT1 target most relevant for the behavioral phenotype.…”

Section: Discussionsupporting

confidence: 81%

“…This is similar to the result reported for TYF, which also supports PER translation in PDF cells (Lim et al 2011). Flies homozygous for the full-length UAS-NAT1 (four gene copies total), however, did have significantly faster rhythms (23.2 hr) and a persistent morning peak ( Figure S3); a truncated version of this transgene missing 59-UTR regions was without effect.…”

Section: Discussionsupporting

confidence: 75%

“…Although we lack evidence for a direct effect of this translation factor on per or tim mRNA, as was provided recently for TYF (Lim et al 2011), our work supports a model in which PER is translated in a noncanonical fashion due in part to NAT1 activity, especially in the PDF clock neurons. Utilization of an atypical translation pathway may be related to the fact that these cells are light sensitive and that light drives intracellular chemical changes that may affect translation (Morse et al 1989;Powley et al 2009).…”

Section: Discussionsupporting

confidence: 60%

“…For example, the DEAD-box helicase Lark delays circadian-gated eclosion until early morning (Newby and Jackson 1993) and influences constant darkness (DD) rhythms (Huang et al 2009). Also, PER translation is stimulated by interactions between its 39-UTR, TYF and PABP (Lim et al 2011). Similar evidence is present in mammalian systems.…”

supporting

confidence: 64%

“…Although we lack evidence for direct interaction, it is possible that NAT1 is present within initiation complexes containing per or tim mRNA and TYF, which was shown to bind both mRNAs (Lim et al 2011). Proof of cap-independent activity for either mRNA would have been striking, but the results were negative for both 59-UTRs in common cellculture and in vitro assays (data not shown).…”

Section: Discussionmentioning

confidence: 83%

See 4 more Smart Citations

NAT1/DAP5/p97 and Atypical Translational Control in the Drosophila Circadian Oscillator

2012

View full text Add to dashboard Cite

Circadian rhythms are driven by gene expression feedback loops in metazoans. Based on the success of genetic screens for circadian mutants in Drosophila melanogaster, we undertook a targeted RNAi screen to study the impact of translation control genes on circadian locomotor activity rhythms in flies. Knockdown of vital translation factors in timeless protein-positive circadian neurons caused a range of effects including lethality. Knockdown of the atypical translation factor NAT1 had the strongest effect and lengthened circadian period. It also dramatically reduced PER protein levels in pigment dispersing factor (PDF) neurons. BELLE (BEL) protein was also reduced by the NAT1 knockdown, presumably reflecting a role of NAT1 in belle mRNA translation. belle and NAT1 are also targets of the key circadian transcription factor Clock (CLK). Further evidence for a role of NAT1 is that inhibition of the target of rapamycin (TOR) kinase increased oscillator activity in cultured wings, which is absent under conditions of NAT1 knockdown. Moreover, the per 59-and 39-UTRs may function together to facilitate cap-independent translation under conditions of TOR inhibition. We suggest that NAT1 and cap-independent translation are important for per mRNA translation, which is also important for the circadian oscillator. A circadian translation program may be especially important in fly pacemaker cells.

show abstract

Section: Discussionsupporting

confidence: 81%

Section: Discussionsupporting

confidence: 75%

Section: Discussionsupporting

confidence: 60%

supporting

confidence: 64%

Section: Discussionmentioning

confidence: 83%

See 3 more Smart Citations

NAT1/DAP5/p97 and Atypical Translational Control in the Drosophila Circadian Oscillator

2012

View full text Add to dashboard Cite

show abstract

Roles of peripheral clocks: lessons from the fly

Yildirim¹,

Curtis

Hwangbo

2021

FEBS Letters

View full text Add to dashboard Cite

To adapt to and anticipate rhythmic changes in the environment such as daily light-dark and temperature cycles, internal timekeeping mechanisms called biological clocks evolved in a diverse set of organisms, from unicellular bacteria to humans. These biological clocks play critical roles in organisms' fitness and survival by temporally aligning physiological and behavioral processes to the external cues. The central clock is located in a small subset of neurons in the brain and drives daily activity rhythms, whereas most peripheral tissues harbor their own clock systems, which generate metabolic and physiological rhythms. Since the discovery of Drosophila melanogaster clock mutants in the early 1970s, the fruit fly has become an extensively studied model organism to investigate the mechanism and functions of circadian clocks. In this review, we primarily focus on D. melanogaster to survey key discoveries and progresses made over the past two decades in our understanding of peripheral clocks. We discuss physiological roles and molecular mechanisms of peripheral clocks in several different peripheral tissues of the fly.

show abstract

Experimental assessment of the network properties of the Drosophila circadian clock

Beckwith

Ceriani

2015

J of Comparative Neurology

View full text Add to dashboard Cite

Circadian rhythms are conserved across kingdoms and coordinate physiology and behavior for appropriate time-keeping. The neuronal populations that govern circadian rhythms are described in many animal models, and the current challenge is to understand how they interact to control overt rhythms, remaining plastic enough to respond and adapt to a changing environment. In Drosophila melanogaster, the circadian network comprises about 150 neurons, and the main synchronizer is the neuropeptide pigment-dispersing factor (PDF), released by the well-characterized central pacemaker neurons, the small ventral lateral neurons (sLNvs). However, the rules and properties governing the communication and coupling between this central pacemaker and downstream clusters are not fully elucidated. Here we genetically manipulate the speed of the molecular clock specifically in the central pacemaker neurons of Drosophila and provide experimental evidence of their restricted ability to synchronize downstream clusters. We also demonstrate that the sLNv-controlled clusters have an asymmetric entrainment range and were able to experimentally assess it. Our data imply that different clusters are subjected to different coupling strengths, and display independent endogenous periods. Finally, the manipulation employed here establishes a suitable paradigm to test other network properties as well as the cell-autonomous mechanisms running in different circadian-relevant clusters.

show abstract

The novel gene twenty-four defines a critical translational step in the Drosophila clock

Cited by 78 publications

References 51 publications

NAT1/DAP5/p97 and Atypical Translational Control in the Drosophila Circadian Oscillator

NAT1/DAP5/p97 and Atypical Translational Control in the Drosophila Circadian Oscillator

Roles of peripheral clocks: lessons from the fly

Experimental assessment of the network properties of the Drosophila circadian clock

Contact Info

Product

Resources

About