20K Papers found (0.025 seconds)

Sun Y et al. (2024) J Cell Biol "A RAB transition orchestrates membrane trafficking in unconventional protein secretion."

Sun Y, Zhang M, Ge L

[

J Cell Biol,

2024]

Rab GTPases function as intracellular molecular switches that regulate vesicular transport. In the current issue, Li et al. (https://doi.org/10.1083/jcb.202306107) revealed RAB-8 to RAB-11 transition governing the unconventional secretion of membrane proteins in the intestinal epithelium of C. elegans.

Sun Y et al. (2005) RNA Biol "A unified mode of epigenetic gene silencing: RNA meets polycomb group proteins."

Sun Y, Zhang H

[

RNA Biol,

2005]

Recently, an essential role for RNA in the epigenetic silencing of genes packaged within heterochromatin in animals has been recognized. The RNA appears to be involved in targeting chromatin remodeling activity to a specific locus and in later maintaining the repressed state of the gene. Epigenetic silencing of Hox cluster genes by the Polycomb group proteins also involves the formation of a stably inherited repressive chromatin structure. Recent studies of the C. elegans PcG gene sop-2 reveled an evolutionarily conserved property of PcG proteins in the binding of RNA, suggesting an important role for RNA in PcG-mediated Hox gene repression.

Sun Y et al. (2023) Nature "m¹A in CAG repeat RNA binds to TDP-43 and induces neurodegeneration."

Yin J, Yuan J, Gu W, Bonini NM, Tang F, Dai H, Wang N, Sun Y, Liu X, Wang Y, Cui Y, Gonzalez G, Yang XW, Dai X, Perlegos AE

[

Nature,

2023]

Microsatellite repeat expansions within genes contribute to a number of neurological diseases1,2. The accumulation of toxic proteins and RNA molecules with repetitive sequences, and/or sequestration of RNA-binding proteins by RNA molecules containing expanded repeats are thought to be important contributors to disease aetiology3-9. Here we reveal that the adenosine in CAG repeat RNA can be methylated to N1-methyladenosine (m1A) by TRMT61A, and that m1A can be demethylated by ALKBH3. We also observed that the m1A/adenosine ratio in CAG repeat RNA increases with repeat length, which is attributed to diminished expression of ALKBH3 elicited by the repeat RNA. Additionally, TDP-43 binds directly and strongly with m1A in RNA, which stimulates the cytoplasmic mis-localization and formation of gel-like aggregates of TDP-43, resembling the observations made for the protein in neurological diseases. Moreover, m1A in CAG repeat RNA contributes to CAG repeat expansion-induced neurodegeneration in Caenorhabditis elegans and Drosophila. In sum, our study offers a new paradigm of the mechanism through which nucleotide repeat expansion contributes to neurological diseases and reveals a novel pathological function of m1A in RNA. These findings may provide an important mechanistic basis for therapeutic intervention in neurodegenerative diseases emanating from CAG repeat expansion.

Sun Y et al. (2025) G3 (Bethesda) "Multiple regulators constrain the abundance of C. elegans DLK-1 in ciliated sensory neurons."

Debnath A, Sun Y, Zhou J, Wang Z, Jin Y, Xie B

[

G3 (Bethesda),

2025]

The conserved MAP3K DLKs are widely known for their functions in synapse formation, axonal regeneration and degeneration, and neuronal survival, notably under traumatic injury and chronic disease conditions. In contrast, their roles in other neuronal compartments are much less explored. Through an unbiased forward genetic screening in C. elegans for altered patterns of GFP-tagged DLK-1 expressed from the endogenous locus, we have recently uncovered a mechanism by which the abundance of DLK-1 is tightly regulated by intraflagellar transport in ciliated sensory neurons. Here, we report additional mutants identified from the genetic screen. Most mutants exhibit increased accumulation of GFP::DLK-1 in sensory endings, and the levels of misaccumulated GFP::DLK-1 are exacerbated by loss of function in cebp-1, the b-Zip transcription factor acting downstream of DLK-1. We identify several new mutations in genes encoding proteins functioning in intraflagellar transport and cilia assembly, in components of BBSome, MAPK-15 and DYF-5 kinases. We report a novel mutation in the chaperone HSP90 that causes misaccumulation of GFP::DLK-1 and up-regulation of CEBP-1 selectively in ciliated sensory neurons. We also find that the guanylate cyclase ODR-1 constrains GFP::DLK-1 abundance throughout cilia and dendrites of AWC neurons. Moreover, in odr-1 mutants, AWC cilia display distorted morphology, which is ameliorated by loss of function in dlk-1 or cebp-1. These data expand the landscape of DLK-1 signaling in ciliated sensory neurons and underscore a high degree of cell- and neurite- specific regulation.

Sun Y et al. (2006) Neurosci Bull "Computational analysis of genetic loci required for synapse structure and function and their corresponding microRNAs in C. elegans."

Zhao YN, Wang DY, Sun Y

[

Neurosci Bull,

2006]

Objective To elucidate the important functions of microRNAs (miRNAs) in regulating synaptic assembly and function, we performed a computational analysis for the genetic loci required for the synaptic structure and function and their corresponding miRNAs in C. elegans. Methods Total 198 genetic loci required for the synaptic structure and function were selected. Sequence alignment was combined with E value evaluation to investigate and identify the possible corresponding miRNAs. Results Total 163 genes among the 198 genetic loci selected have their possibly corresponding regulatory miRNA (s), which covered most of the important genetic loci required for the synaptic structure and function. Moreover, only 22 genes among the analyzed 38 genetic loci encoding synaptic proteins have more possibility to under the control of non-coding RNA genes. In addition, the distribution of miRNAs along the 3' untranslated region (UTR) of these 22 genes exhibits different patterns. Conclusion Here we provide the computational screen and analysis results for the genetic loci required for synaptic structure and function and their possible corresponding miRNAs. These data will be useful for the further attempt to systematically determine the roles of miRNAs in synaptic assembly and function regulation in worms.

Sun Y et al. (2020) Elife "Lysosome activity is modulated by multiple longevity pathways and is important for lifespan extension in C. elegans."

Li X, Zhao D, Li M, Sun Y, Wang X, Yang C

[

Elife,

2020]

Lysosomes play important roles in cellular degradation to maintain cell homeostasis. In order to understand whether and how lysosomes alter with age and contribute to lifespan regulation, we characterized multiple properties of lysosomes during the aging process in C. elegans. We uncovered age-dependent alterations in lysosomal morphology, motility, acidity and degradation activity, all of which indicate a decline in lysosome function with age. The age-associated lysosomal changes are suppressed in the long-lived mutants daf-2, eat-2 and isp-1, which extend lifespan by inhibiting insulin/IGF-1 signaling, reducing food intake and impairing mitochondrial function, respectively. We found that 43 lysosome genes exhibit reduced expression with age, including genes encoding subunits of the proton pump V-ATPase and cathepsin proteases. The expression of lysosome genes is upregulated in the long-lived mutants, and this upregulation requires the functions of DAF-16/FOXO and SKN-1/NRF2 transcription factors. Impairing lysosome function affects clearance of aggregate-prone proteins and disrupts lifespan extension in daf-2, eat-2 and isp-1 worms. Our data indicate that lysosome function is modulated by multiple longevity pathways and is important for lifespan extension.

Sun Y et al. (2020) Sci Rep "Single-cell RNA profiling links ncRNAs to spatiotemporal gene expression during C. elegans embryogenesis."

Mei Z, Wu L, Liu S, Lei Y, Drmanac R, Sun Y, Liu L, Yu Q, Ma K, Zhou B, Pan T, Li L

[

Sci Rep,

2020]

Recent studies show that non-coding RNAs (ncRNAs) can regulate the expression of protein-coding genes and play important roles in mammalian development. Previous studies have revealed that during C. elegans (Caenorhabditis elegans) embryo development, numerous genes in each cell are spatiotemporally regulated, causing the cell to differentiate into distinct cell types and tissues. We ask whether ncRNAs participate in the spatiotemporal regulation of genes in different types of cells and tissues during the embryogenesis of C. elegans. Here, by using marker-free full-length high-depth single-cell RNA sequencing (scRNA-seq) technique, we sequence the whole transcriptomes from 1031 embryonic cells of C. elegans and detect 20,431 protein-coding genes, including 22 cell-type-specific protein-coding markers, and 9843 ncRNAs including 11 cell-type-specific ncRNA markers. We induce a ncRNAs-based clustering strategy as a complementary strategy to the protein-coding gene-based clustering strategy for single-cell classification. We identify 94 ncRNAs that have never been reported to regulate gene expressions, are co-expressed with 1208 protein-coding genes in cell type specific and/or embryo time specific manners. Our findings suggest that these ncRNAs could potentially influence the spatiotemporal expression of the corresponding genes during the embryogenesis of C. elegans.

Sun Y et al. (2025) Eur J Pharmacol "Cordycepin Extends the Longevity of Caenorhabditis elegans via Antioxidation and Regulation of Fatty Acid Metabolism."

Han Z, Zhang Q, Shen C, Zhong M, Cao X, Feng M, Wang J, Sun Y

[

Eur J Pharmacol,

2025]

Aging can cause age-related diseases such as cancer, cardiovascular and neurodegenerative diseases. Cordycepin exerts anti-oxidation, anti-inflammatory and neuroprotective effects. However, the anti-aging effect of cordycepin is still unclear. This study aimed to investigate the anti-aging effect of cordycepin and unravel the underlying mechanism. Cordycepin prolonged the lifespan of C. elegans under normal and heat stress conditions, without effects on the normal growth and reproduction of C. elegans. Cordycepin also improved the locomotion ability, inhibited the deposition of aging pigment lipofuscin and alleviated the oxidative stress damage by decreasing the excessive accumulation of ROS and raising the antioxidant enzyme activities in C. elegans. The metabolomics study showed that cordycepin changed 19 metabolites including citric acid, linoleic acid, oleic acid, glutamic acid, pyruvic acid and so on. Transcriptomics study revealed that cordycepin up-regulated the gene expression of acox-1.2, acox-1.3, acox-1.4, acs-1, acs-15, acdh-1, acdh-4 and acdh-8 in C. elegans, suggesting that cordycepin prolonged its lifespan via regulating fatty acid degradation, fatty acid metabolism and so on. In summary, the current study demonstrated that cordycepin exerted the anti-aging effect on C. elegans by improving the antioxidant system and regulating the genes involved in fatty acid metabolism to inhibit the accumulation of linoleic acid and oleic acid. Therefore, cordycepin might be a promising agent for aging and age-related diseases.

Sun Y et al. (2024) MicroPubl Biol "Loss of function in rpms-1 does not enhance phenotypes of rpm-1 mutants."

Noma K, Jin Y, Xie B, Sun Y, Gaio D, Wu Z

[

MicroPubl Biol,

2024]

The C. elegans E3 ubiquitin ligase RPM-1 consists of 3,766 amino acids, with a RING finger domain at the C-terminus that functions to target the DLK-1 kinase for degradation for synapse development and axon termination. rpms-1 ( for rpm-1 short, aka F07B7.12 ) resides 35 kb away from rpm-1 on chromosome V, and is a near-perfect 12 kb duplication of rpm-1 , including the entire promoter region and coding sequences. RPMS-1 consists of 1,964 amino acids and is identical to the N-terminal half of RPM-1 , except the last 40 amino acids. Previous studies showed that transgenic overexpression of the duplicated region of rpm-1 (+) did not rescue synapse defects of rpm-1 loss of function mutants. Here, using CRISPR editing, we generated a double knockout of rpm-1 and rpms-1 . We find that axon and synapse defects in rpm-1rpms-1 double mutants resemble those in rpm-1 single mutants. Expression levels of endogenously tagged DLK-1 protein are increased to a comparable degree in rpm-1 and rpm-1rpms-1 mutants, compared to the control. These data, along with previous transgene expression analysis, support the idea that rpms-1 does not have a major role in RPM-1-mediated cellular processes.

Sun Y et al. (2013) PLoS One "The F-box protein MEC-15 (FBXW9) promotes synaptic transmission in GABAergic motor neurons in C. elegans."

Sun Y, Goeb Y, Dreier L, Hu Z

[

PLoS One,

2013]

Ubiquitination controls the activity of many proteins and has been implicated in almost every aspect of neuronal cell biology. Characterizing the precise function of ubiquitin ligases, the enzymes that catalyze ubiquitination of target proteins, is key to understanding distinct functions of ubiquitination. F-box proteins are the variable subunits of the large family of SCF ubiquitin ligases and are responsible for binding and recognizing specific ubiquitination targets. Here, we investigated the function of the F-box protein MEC-15 (FBXW9), one of a small number of F-box proteins evolutionarily conserved from C. elegans to mammals. mec-15 is widely expressed in the nervous system including GABAergic and cholinergic motor neurons. Electrophysiological and behavioral analyses indicate that GABAergic synaptic transmission is reduced in mec-15 mutants while cholinergic transmission appears normal. In the absence of MEC-15, the abundance of the synaptic vesicle protein SNB-1 (synaptobrevin) is reduced at synapses and increased in cell bodies of GABAergic motor neurons, suggesting that MEC-15 affects the trafficking of SNB-1 between cell bodies and synapses and may promote GABA release by regulating the abundance of SNB-1 at synapses.

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