Infarinato N (2019) J Cell Biol "Xiaochen Wang: Building up our understanding of breaking down."

Infarinato N

[J Cell Biol, 2019]

Wang studies lysosomal degradation pathways using <i>C. elegans</i> as a model system.

Wang JT et al. (2014) Curr Biol "P granules."

Wang JT, Seydoux G

[Curr Biol, 2014]

Wang and Seydoux discuss the functional importance of P granules - the germline-specific RNA granules of C. elegans.

Rashid S et al. (2017) Dev Cell "Packing on the Pounds in Response to Bacterial Growth Conditions."

Rashid S, MacNeil LT

[Dev Cell, 2017]

Reporting in Nature Cell Biology, Lin and Wang (2017) show that bacterial methyl metabolism impacts host mitochondrial dynamics and lipid storage in C.elegans. The authors propose a model whereby bacterial metabolic products regulate a nuclear hormone receptor that promotes lipid accumulation through expression of a secreted Hedgehog-like protein.

Munro E (2017) Dev Cell "Protein Clustering Shapes Polarity Protein Gradients."

Munro E

[Dev Cell, 2017]

In this issue of Developmental Cell, Dickinson etal. (2017) and Rodriguez etal. (2017), along with Wang etal. (2017) in Nature Cell Biology, show how PAR protein oligomerization can dynamically couple protein diffusion and transport by cortical flow to control kinase activity gradients and polarity in the C.elegans zygote.

Vincenz L et al. (2014) Cell "Sugarcoating ER Stress."

Hartl FU, Vincenz L

[Cell, 2014]

The hexosamine biosynthetic pathway (HBP) generates metabolites for protein N- and O-glycosylation. Wang et al. and Denzel et al. report a hitherto unknown link between the HBP and stress in the endoplasmic reticulum. These studies establish the HBP as a critical component of the cellular machinery of protein homeostasis.

Sural S (2023) Trends Genet "Protecting axons in grandchildren."

Sural S

[Trends Genet, 2023]

Prenatal exposure to environmental agents can influence the fitness of not only the fetus, but also subsequent generations. In a recent study, Wang et al. demonstrated that feeding ursolic acid (UA), a plant-derived compound, to Caenorhabditis elegans mothers during their reproductive period prevented neurodegeneration in not only their offspring, but also the F2 progeny.

Spalthoff C et al. (2016) Neuron "Sensing pH with TMCs."

Gopfert MC, Spalthoff C

[Neuron, 2016]

Transmembrane channel-like (TMC) proteins have been implicated in hair cell mechanotransduction, Drosophila proprioception, and sodium sensing in the nematode C.elegans. In this issue of Neuron, Wang etal. (2016) report that C.elegans TMC-1 mediates nociceptor responses to high pH, not sodium, allowing the nematode to avoid strongly alkaline environments in which most animals cannot survive.

Wu, Monica et al. (2013) International Worm Meeting "Functional Characterization of the CSR-1 Small RNA Pathway in C. briggsae."

Weng, Zhiping, Wu, Monica, Tu, Shikui, Wang, Jie, Claycomb, Julie M.

[International Worm Meeting, 2013]

When Sydney Brenner chose C. elegans as a model, he set the stage for a series of discoveries that have transformed molecular biology: the discovery of RNA interference (RNAi) and endogenous small RNA pathways, including microRNAs. One of Brenner's alternative nematode species, C. briggsae has come into common use during the genomics era and affords the ability to perform comparative genomics studies on a range of questions. Recently several studies have delved into small RNA pathways in C. briggsae, cataloging classes of small RNAs from sequencing data, and identifying conserved Argonaute proteins by sequence homology. However, the function of any Argonaute/small pathway in C. briggsae has yet to detailed. Here we characterize the functions of an essential Argonaute, CSR-1 (Chromosome Segregation and RNAi Deficient) in C. briggsae. CbCSR-1 was an attractive candidate for our studies because: 1. An antibody against CeCSR-1 could recognize CbCSR-1 and 2. CeCSR-1 has been shown to target approximately 4200 germline-expressed protein coding genes via 22G-RNAs to regulate chromatin and impact chromosome segregation. We used Illumina sequencing to identify the small RNA complement associated with CbCSR-1 and examined small RNA populations in worms in which cbcsr-1 was depleted by RNAi. We find that the small RNAs enriched in CSR-1 complexes overlap with those depleted under cbcsr-1 RNAi conditions, establishing a high-confidence set of CbCSR-1-dependent small RNAs. We have compared the CbCSR-1 and CeCSR-1 target transcripts to define conserved characteristics that contribute to a transcript becoming the target of the CSR-1 pathway. Finally, we have determined that CbCSR-1 associates with germline and embryonic chromatin, and we demonstrate that depletion of cbcsr-1 leads to chromosome segregation defects, like its C. elegans ortholog. In sum, this is the first characterization of an Argonaute/small RNA pathway in C. briggsae, whereby we demonstrate a conserved, role for the CSR-1 pathway and emphasize that this pathway plays a role in chromosome segregation in multiple animal species.

Wu, Monica et al. (2015) International Worm Meeting "Comparative Functional Characterization of the CSR-1 22G-RNA Pathway in Caenorhabditis."

Julie, Claycomb, Weng, Zhiping, Wu, Monica, Wang, Jie, Cutter, Asher, Tu, Shikui

[International Worm Meeting, 2015]

As a champion of small RNA research for two decades, C. elegans has revealed the essential Argonaute CSR-1 to play key nuclear roles in modulating chromatin, chromosome segregation, and germline gene expression via 22G-small RNAs. Despite CSR-1 being preserved among diverse nematodes (Clade III and Clade V), the conservation and divergence in function of the targets of small RNA pathways remains poorly resolved. Here we apply comparative functional genomic analysis between C. elegans and C. briggsae to characterize the CSR-1 small RNA pathway, its targets, and their evolution. C. briggsae CSR-1-associated small RNAs that we identified by immunoprecipitation-small RNA sequencing overlap with 22G-RNAs depleted in cbr-csr-1 RNAi-treated worms. Notably, our analysis of CSR-1 associated small RNAs in C. briggsae revealed a previously unappreciated class of 22A-RNAs that are also present in C. elegans. By comparing 22G-RNAs and target genes between species, we defined a set of CSR-1 target genes mostly with conserved germline expression, enrichment in operons, and more slowly-evolving coding sequences than other germline genes, along with a small group of evolutionarily labile targets. We demonstrate that the association of CSR-1 with chromatin is preserved between species, and show that depletion of cbr-csr-1 leads to chromosome segregation defects and embryonic lethality. This first comparative characterization of a small RNA pathway in Caenorhabditis establishes a conserved nuclear role for CSR-1 and highlights its key role in germline gene regulation across multiple animal species.

Matsumoto M et al. (2005) Cell Metab "All roads lead to FoxO."

Accili D, Matsumoto M

[Cell Metab, 2005]

Stress-activated kinases control metabolism by antagonizing the early steps of insulin signal transduction. Two papers now demonstrate that Jnk, the prototypical stress-activated kinase, controls life span in Drosophila and C. elegans by promoting phosphorylation of the forkhead protein FoxO (Oh et al., 2005; Wang et al., 2005). The findings provide yet another mechanism by which metabolic and stress responses are integrated via phosphorylation of FoxO proteins.