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57
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1,886
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Citations since 2017
Introduction
Additional affiliations
March 2013 - February 2017
March 2007 - February 2013
Publications
Publications (57)
Significance
Foraging and sleep are two conflicting behaviors in starved animals; however, it remains elusive how metabolic status governs sleep drive. In this study, we show that a biosynthetic pathway for the amino acid serine is transcriptionally up-regulated by starvation in adult fly brains. The behavioral response to genetic manipulation of k...
Emerging evidence indicates the role of amino acid metabolism in sleep regulation. Here we demonstrate sleep-promoting effects of dietary threonine (SPET) in Drosophila. Dietary threonine markedly increased daily sleep amount and decreased the latency to sleep onset in a dose-dependent manner. High levels of synaptic GABA or pharmacological activat...
Sleep behaviors are observed even in nematodes and arthropods, yet little is known about how sleep-regulatory mechanisms have emerged during evolution. Here, we report a sleep-like state in the cnidarian Hydra vulgaris with a primitive nervous organization. Hydra sleep was shaped by homeostasis and necessary for cell proliferation, but it lacked fr...
Nucleocytoplasmic transport (NCT) defects have been implicated in neurodegenerative diseases such as C9ORF72 -associated amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). Here, we identify a neuroprotective pathway of like-Sm protein 12 ( LSM12 ) and exchange protein directly activated by cyclic AMP 1 ( EPAC1 ) that sustains t...
C9ORF72-derived dipeptide repeat proteins have emerged as the pathogenic cause of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). However, the mechanisms underlying their expression are not fully understood. Here, we demonstrate that ZNF598, the rate-limiting factor for ribosome-associated quality contro...
Thermal stress induces dynamic changes in nuclear proteins and relevant physiology as a part of the heat shock response (HSR). However, how the nuclear HSR is fine-tuned for cellular homeostasis remains elusive. Here, we show that mitochondrial activity plays an important role in nuclear proteostasis and genome stability through two distinct HSR pa...
Circadian rhythms and sleep homeostasis constitute the two-process model for daily sleep regulation. However, evidence for circadian control of sleep-wake cycles has been relatively short since clock-less animals often show sleep behaviors quantitatively comparable to wild-type. Here we examine Drosophila sleep behaviors under different light-dark...
Background
The establishment and maintenance of functional neural connections relies on appropriate distribution and localization of mitochondria in neurites, as these organelles provide essential energy and metabolites. In particular, mitochondria are transported to axons and support local energy production to maintain energy-demanding neuronal pr...
The pioneer (or first) round of translation of newly synthesized mRNAs is largely mediated by a nuclear cap-binding complex (CBC). In a transcriptome-wide analysis of polysome-associated and CBC-bound transcripts, we identify RN7SL1, a noncoding RNA component of a signal recognition particle (SRP), as an interaction partner of the CBC. The direct C...
Significance
In animals, the control of daily sleep–wake rhythms is mediated by discrete circadian clock neurons via their rhythmic activity–dependent release of neuropeptides and neurotransmitters. Here, we describe a gene, Tango10 , critical for daily behavioral rhythms. TANGO10 functions as an adaptor with its partner, the E3 ubiquitin ligase CU...
Kohlschütter-Tönz syndrome (KTS) manifests as neurological dysfunctions, including early-onset seizures. Mutations in the citrate transporter SLC13A5 are associated with KTS, yet their underlying mechanisms remain elusive. Here, we report that a Drosophila SLC13A5 homolog, I’m not dead yet ( Indy ), constitutes a neurometabolic pathway that suppres...
Translating ribosomes accompany co-translational regulation of nascent polypeptide chains, including subcellular targeting, protein folding, and covalent modifications. Ribosome-associated quality control (RQC) is a co-translational surveillance mechanism triggered by ribosomal collisions, an indication of atypical translation. The ribosome-associa...
Mitochondrial initiation factor 3 (mtIF3) binds to and dissociates mitochondrial ribosomes. The mtIF3- small subunit complex then recruits mtIF2, mRNA, and N-formylmethionine-tRNA to initiate mitochondrial translation. Intriguingly, transcripts of the nuclear-encoded mtIF3 gene have been shown present in axonal growth cones; however, the biological...
Genes and neural circuits coordinately regulate animal sleep. However, it remains elusive how these endogenous factors shape sleep upon environmental changes. Here, we demonstrate that Shaker (Sh)-expressing GABAergic neurons projecting onto dorsal fan-shaped body (dFSB) regulate temperature-adaptive sleep behaviors in Drosophila. Loss of Sh functi...
Circadian gene expression is defined by the gene-specific phase and amplitude of daily oscillations in mRNA and protein levels. D site-binding protein ( Dbp ) mRNA shows high-amplitude oscillation, however, the underlying mechanism remains elusive. Here, we demonstrate that heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a key regulator that...
Disrupted circadian rhythms is a prominent and early feature of neurodegenerative diseases including Huntington’s disease (HD). In HD patients and animal models, striatal and hypothalamic neurons expressing molecular circadian clocks are targets of mutant Huntingtin (mHtt) pathogenicity. Yet how mHtt disrupts circadian rhythms remains unclear. In a...
Post-transcriptional regulation underlies the circadian control of gene expression and animal behaviors. However, the role of mRNA surveillance via the nonsense-mediated mRNA decay (NMD) pathway in circadian rhythms remains elusive. Here, we report that Drosophila NMD pathway acts in a subset of circadian pacemaker neurons to maintain robust 24 h r...
Post-transcriptional regulation underlies the circadian control of gene expression and animal behaviors. However, the role of mRNA surveillance via the nonsense-mediated mRNA decay (NMD) pathway in circadian rhythms remains elusive. Here, we report that Drosophila NMD pathway acts in a subset of circadian pacemaker neurons to maintain robust 24h rh...
Ataxin‐2 (ATXN2) is a eukaryotic RNA‐binding protein that is conserved from yeast to human. Genetic expansion of a poly‐glutamine tract in human ATXN2 has been implicated in several neurodegenerative diseases, likely acting through gain‐of‐function effects. Emerging evidence, however, suggests that ATXN2 plays more direct roles in neural function v...
Post-translational control is a crucial mechanism for circadian timekeeping. Evolutionarily conserved kinases and phosphatases have been implicated in circadian phosphorylation and the degradation of clock-relevant proteins, which sustain high-amplitude rhythms with 24-hr periodicity in animal behaviors and physiology. Here, we report a novel clock...
Kohlschutter-Tönz syndrome (KTS) is a rare genetic disorder with neurological dysfunctions including seizure and intellectual impairment. Mutations at the Rogdi locus have been linked to development of KTS, yet the underlying mechanisms remain elusive. Here we demonstrate that a Drosophila homolog of Rogdi acts as a novel sleep-promoting factor by...
Kohlschutter-Tönz syndrome (KTS) is a rare autosomal-recessive disorder of childhood onset characterized by global developmental delay, spasticity, epilepsy, and amelogenesis imperfecta. Rogdi, an essential protein, is highly conserved across metazoans, and mutations in Rogdi are linked to KTS. However, how certain mutations in Rogdi abolish its ph...
ATAXIN-2 (ATX2) has been implicated in human neurodegenerative diseases, yet it remains elusive how ATX2 assembles specific protein complexes to execute its physiological roles. Here we employ the posttranscriptional co-activator function of Drosophila ATX2 to demonstrate that LSM12 and ME31B/DDX6 are two ATX2-associating factors crucial for sustai...
Light is one of the strongest environmental time cues for entraining endogenous circadian rhythms. Emerging evidence indicates that CREB-regulated transcription co-activator 1 (CRTC1) is a key player in this pathway, stimulating light-induced Period1 (Per1) transcription in mammalian clocks. Here, we demonstrate a light-independent role of Drosophi...
Circadian clocks are endogenous time-keeping mechanisms to adaptively coordinate animal behaviors and physiology with daily environmental changes. So far many circadian studies in model organisms have identified evolutionarily conserved molecular frames of circadian clock genes in the context of transcription-translation feedback loops. The molecul...
SIFamide receptor (SIFR) is a Drosophila G protein-coupled receptor for the neuropeptide SIFamide (SIFa). Although the sequence and spatial expression of SIFa are evolutionarily conserved among insect species, the physiological function of SIFa/SIFR signaling remains elusive. Here, we provide genetic evidence that SIFa and SIFR promote sleep in Dro...
Circadian clocks temporally organize behavior and physiology across the 24-h day. Great progress has been made in understanding the molecular basis of timekeeping, with a focus on transcriptional feedback networks that are post-translationally modulated. Yet emerging evidence indicates an important role for post-transcriptional regulation, from spl...
ATAXIN Clock
Although core components of circadian clocks in flies and mammals are transcriptional circuits, recent evidence indicates posttranscriptional regulation of the clock occurs. Studies from Lim and Allada (p. 875 ) and Zhang et al. (p. 879 ) converge to show that the protein ATAXIN-2, associated with neurodegenerative diseases in humans,...
Daily oscillations of gene expression underlie circadian behaviours in multicellular organisms. While attention has been focused on transcriptional and post-translational mechanisms, other post-transcriptional modes have been less clearly delineated. Here we report mutants of a novel Drosophila gene twenty-four (tyf) that show weak behavioural rhyt...
During latent infection, latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays important roles in episomal persistence and replication. Several host factors are associated with KSHV latent replication. Here, we show that the catalytic subunit of DNA protein kinase (DNA-PKcs), Ku70, and Ku86 bind the N-ter...
Reversible phosphorylation of clock proteins plays an important role in circadian timekeeping as it is a key post-translational mechanism that regulates the activity, stability and subcellular localization of core clock proteins. The kinase DOUBLETIME (DBT), a Drosophila ortholog of mammalian casein kinase Iepsilon, regulates circadian phosphorylat...
vrille and Par domain protein 1 (Pdp1) epsilon constitute the second transcriptional feedback loop in Drosophila circadian clock system. Their rhythmic expression is controlled by Drosophila Clock (dClk) gene, and they feed back to negatively and positively, respectively, regulate the oscillating transcription from dClk gene. In this study, we char...
Rhythmic histone acetylation underlies the oscillating expression of clock genes in the mammalian circadian clock system.
Cellular factors that contain histone acetyltransferase and histone deacetylase activity have been implicated in these processes
by direct interactions with clock genes, but their functional relevance remains to be assessed by u...
Gene transcription is a central timekeeping process in animal clocks. In Drosophila, the basic helix-loop helix (bHLH)-PAS transcription-factor heterodimer, CLOCK/CYCLE (CLK/CYC), transcriptionally activates the clock components period (per), timeless (tim), Par domain protein 1 (Pdp1), and vrille (vri), which feed back and regulate distinct featur...
Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays an important role in the immune system and cell death. Many viral proteins modulate NF-kappaB to escape host immune surveillance, promote cell survival, and enhance viral replication. In the present study, we show that NF-kappaB activity is downmodulated by viral interferon regu...
Latency-associated
nuclear antigen 1 (LANA1) of Kaposi's sarcoma-associated
herpesvirus (KSHV) is implicated in the persistence of the viral genome
during latent infection. It has been suggested that LANA1 tethers the
viral genome to the host chromosome and also participates actively in
DNA replication from the terminal repeat of KSHV. Here we show...
Latency-associated nuclear antigen 1 (LANA1) of Kaposi's sarcoma-associated herpesvirus (KSHV) plays a pivotal role in the maintenance of the virus genome in latently infected cells. LANA1 links virus genomes to host chromosomes via a C-terminal DNA-binding domain which interacts with the sequences located in terminal repeats (TRs) of the virus gen...
Latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus plays an important role in maintenance of the viral genome during latent infection. LANA additionally participates in the transcriptional regulation of several viral and cellular promoters. When tethered to constitutively active promoters, the protein exhibits tran...
The cytoskeletal matrix assembled at active zones (CAZ) is implicated in defining neurotransmitter release sites. However, little is known about the molecular mechanisms by which the CAZ is organized. Here we report a novel interaction between Piccolo, a core component of the CAZ, and GIT proteins, multidomain signaling integrators with GTPase-acti...
BRG-1, a component of the human SWI/SNF complex, either activates or represses cellular promoters by modulating chromatin
structure via the formation of a multiple polypeptide complex. Human papillomavirus E7 binds and destabilizes pRb, resulting
in the blockage of G1 arrest in the cell cycle. We show here that the high-risk human papillomavirus E7...
Latency-associated nuclear antigen 1 (LANA1) of Kaposi's sarcoma-associated herpesvirus (KSHV) is implicated in the maintenance
of the viral genome during latent infection. LANA1 colocalizes with KSHV episomes on the host chromosome and mediates their
maintenance by attaching these viral structures to host chromosomes. Data from long-term selection...
Kaposi's sarcoma-associated herpesvirus (KSHV) is an important pathogen in Kaposi's sarcoma and abnormal lymphoproliferation.
KSHV open reading frame 50 (ORF50), a homolog of the Epstein-Barr virus immediate-early gene product RTA, activates early
and late gene transcription in the KSHV lytic cycle, and its expression is closely correlated with KSH...
Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame K8 encodes a basic region-leucine zipper protein of 237
amino acids that homodimerizes with its bZIP domain. KSHV K8 shows significant homology to the Epstein-Barr virus (EBV) immediate-early
protein Zta, a key regulator in the reactivation and replication of EBV. In this study, we r...
A multifunctional transcription co-activator, cAMP response element-binding protein-binding protein (CBP)interacts with a number of cellular factors and participates in cell growth, transformation, and development. It is also targeted by many viral proteins for their transcriptional activity or for the regulation of cellular processes. Here, we rep...
Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 50 (ORF50) encodes a viral transcriptional activator which
stimulates the transcription of viral early and late genes of KSHV. Here we show that ORF50 represses transcriptional activity
of p53 and p53-induced apoptosis through interaction with CREB binding protein (CBP). This inhibit...
Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) open reading frame 50 (ORF50) encodes a viral transcriptional activator, which binds to the KSHV promoter and stimulates the transcription of viral early and late genes, thus activating the lytic cycle of KSHV. We report here that KSHV ORF50 binds to the cellular proteins CREB-binding protein (CBP...
Latency-associated nuclear antigen (LANA), encoded by ORF 73 of Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus-8), may play an important role in the persistence of the viral episome by tethering it to host chromosomes during mitosis. It also has been suggested from its amino acid sequence features that LANA may have transcription-...
