Chen MX et al. (2011) Parasitol Res "Identification and characterization of microRNAs in Trichinella spiralis by comparison with Brugia malayi and Caenorhabditis elegans."

Xu MJ, Chen MX, Zhang YN, Zhang LL, Ai L, Chen SH, Tian LG, Chen JX, Guo J, Cai YC, Zhu XQ

[Parasitol Res, 2011]

Trichinella spiralis is an important zoonotic nematode causing trichinellosis which is associated with human diseases such as malaise, anorexia, nausea, vomiting, abdominal pain, fever, diarrhea, and constipation. microRNAs (miRNAs) are endogenous small non-coding RNAs that play important roles in the regulation of gene expression. The objective of the present study was to examine the miRNA expression profile of the larvae of T. spiralis by Solexa deep sequencing combined with stem-loop real-time polymerase chain reaction (PCR) analysis. T. spiralis larvae were collected from the skeletal muscle of naturally infected pigs in Henan province, China, by artificial digestion using pepsin. The specific identity of the T. spiralis larvae was confirmed by PCR amplification and subsequent sequence analysis of the internal transcribed spacer of ribosomal DNA. A total of 17,851,693 reads with 2,773,254 unique reads were obtained. Eleven conserved miRNAs from 115 unique xsmall RNAs (sRNAs) and 12 conserved miRNAs from 130 unique sRNAs were found by BLAST analysis against the known miRNAs of Caenorhabditis elegans ( ftp://ftp.ncbi.nih.gov/genomes/Caenorhabditis_elegans ) and Brugia malayi dataset ( http://www.ncbi.nlm.nih.gov/genomeprj?Db=genomeprj&cmd=ShowDetailView&TermToSearch=9549 ) in miRBase, respectively. One novel miRNA with 12 precursors were identified and certified using the reference genome of B. malayi, while no novel miRNA was found when using the reference genome of C. elegans. Nucleotide bias analysis showed that the uracil was the prominent nucleotide, particularly at the 1st, 6th, 18th, and 23th positions, which were almost at the beginning, middle, and the end of the conserved miRNAs. The identification and characterization of T. spiralis miRNAs provides a new resource to study regulation of genes and their networks in T. spiralis.

Wang S et al. (2001) EMBO J "The TRA-1 transcription factor binds TRA-2 to regulate sexual fates in Caenorhabditis elegans."

Wang S, Kimble J

[EMBO J, 2001]

The tra-1 and tra-2 sex-determining genes promote female fates in Caenorhabditis elegans. Classical genetic studies placed tra-1 as the terminal regulator of the pathway with tra-2 acting upstream as a regulator of regulators of tra-1. Here we report the surprising result that the TRA-1 transcription factor binds the intracellular domain of the TRA-2 membrane protein. This binding is dependent on the MX regulatory domain, a region of the TRA-2 intracellular domain shown previously to be critical for the onset of hermaphrodite spermatogenesis. The functional importance of the TRA-1-TRA-2 physical interaction is supported by genetic interactions between tra-1(0) and tra-2(mx) mutations: a reduction of tra-1 gene dose from two copies to one copy enhances the tra-2(mx) feminization phenotype, but has no apparent somatic effect. In Caenorhabditis briggsae, we also find an MX-dependent interaction between Cb-TRA-1 and Cb-TRA-2, hut intriguingly, no cross-species interactions are seen. The conservation of the TRA-1-TRA-2 interaction underscores its importance in sex determination.

Po MD et al. (2012) Neuron "Releasing the inner inhibition for axon regeneration."

Po MD, Calarco JA, Zhen M

[Neuron, 2012]

The adult mammalian central nervous system exhibits restricted regenerative potential. Chen etal. (2011) and El Bejjani and Hammarlund (2012) used Caenorhabditis elegans to uncover intrinsic factors that inhibit regeneration of axotomized mature neurons, opening avenues for potential therapeutics.

Kuwabara PE et al. (1998) Dev Biol "Germ-line regulation of the Caenorhabditis elegans sex-determining gene tra-2."

Kuwabara PE, Kimble JE, Okkema PG

[Dev Biol, 1998]

The Caenorhabditis elegans sex-determining gene tra-2 promotes female development of the XX hermaphrodite soma and germ line. We previously showed that a 4.7-kb tra-2 mRNA, which encodes the membrane protein TRA-2A, provides the primary feminizing activity of the tra-2 locus. This paper focuses on the germ-line activity and regulation of tra-2. First, we characterize a 1.8-kb tra-2 mRNA, which is hermaphrodite-specific and germ-line-dependent. This mRNA encodes TRA-2B, a protein identical to a predicted intracellular domain of TRA-2A. We show that the 1.8-kb mRNA is oocyte-specific, suggesting that it is involved in germ-line or embryonic sex determination. Second, we identify a tra-2 maternal effect on brood size that may be associated with the 1.8-kb mRNA. Third, we investigate seven dominant tra-2(mx) (for mixed character) mutations that sexually transform hermaphrodites to females by eliminating hermaphrodite spermatogenesis. Each of the tra-2(mx) mutants possesses a nonconserved missense change in a 22-amino-acid region common to both TRA-2A and TRA-2B, called the MX region. We propose that the MX region mediates a posttranslational regulation of tra-2 essential for the onset of hermaphrodite spermatogenesis. Finally, we discuss aspects of tra-2 function and regulation that are specific to the unusual control of cell fate in the hermaphrodite germ line.

Silverstein NJ et al. (2017) Immunity "Interleukin-17: Why the Worms Squirm."

Huh JR, Silverstein NJ

[Immunity, 2017]

IL-17 is a cytokine known primarily for its role in inflammation. In a recent issue of Nature, Chen etal. (2017) demonstrate that IL-17 plays a neuromodulatory role in Caenorhabditis elegans by acting directly on neurons to amplify neuronal responses to stimuli and produce changes in animal behavior.

Artan M et al. (2016) Dev Cell "Heat FLiPs a Hormonal Switch for Longevity."

Lee SV, An SW, Artan M

[Dev Cell, 2016]

Temperature-sensing neurons in C.elegans reduce the life-shortening effects of high temperatures via steroid signaling. In this issue of Developmental Cell, Chen etal. (2016) elucidate the underlying mechanisms by which the transcription factor CREB induces the neuropeptide FLP-6 in the temperature-sensing neurons to counteract the life-shortening effects of high temperature.

Akin O et al. (2014) Cell "The shape of things to come."

Akin O, Zipursky SL

[Cell, 2014]

Surface receptors can link binding of ligands to changes in the actin-based cell cytoskeleton. Chia etal. and Chen etal. provide evidence for direct binding between the cytoplasmic tails ofreceptorsand the WAVE complex, a regulator of the actin nucleator Arp2/3 complex, which mighthelp to explain how environmental signals are translated into changes in morphology andmotility.

Chen X et al. (2015) Mol Neurodegener "Erratum to: Ethosuximide ameliorates neurodegenerative disease phenotypes by modulating DAF-16/FOXO target gene expression."

McCue HV, Chen X, Morgan A, Kashyap SS, Barclay JW, Kraemer BC, Burgoyne RD, Wong SQ

[Mol Neurodegener, 2015]

The original version of this article [1] unfortunately contained a mistake. The author list contained a spelling error for the author Hannah V. McCue. The original article has been corrected for this error. The corrected author list is given below:Xi Chen, Hannah V. McCue, Shi Quan Wong, Sudhanva S. Kashyap, Brian C. Kraemer, Jeff W. Barclay, Robert D. Burgoyne and Alan Morgan

Kuwabara PE (1996) Genetics "Interspecies comparison reveals evolution of control regions in the nematode sex-determining gene tra-2."

Kuwabara PE

[Genetics, 1996]

The Caenorhabditis elegans sex-determining gene tra-2 promotes female development and expresses 4.7-, 1.9- and 1.8-kb mRNAs. The 4.7-kb mRNA encodes the major feminizing activity of the locus, a predicted membrane receptor that mediates cell-to-cell communication, named TRA-2A. The tra-2 gene was characterized from a close relative, C. briggsae. The Cb-tra-2 gene expresses only a 4.7-kb mRNA and alternatively spliced variants, which encode TRA-2A homologues. The Cb-TRA-2A and Ce-TRA-2A sequences are highly diverged, sharing only 43% identity, although their hydropathy profiles remain remarkably similar. Three potential regulatory sites of Ce-tra-2 activity were previously identified by analyzing tra-2(eg), tra-2(gf), and tra-2(mx) mutations. Two of these sites, the EG site and MX region, are conserved in Cb-tra-2. By contrast, the two direct repeat elements in the Ce-tra-2 3' untranslated region, which are disrupted in tra-2(gf) mutants, are absent. Injection of Cb-tra-2 antisense RNA into C.briggsae mimics the Ce-tra-2 loss-of-function phenotype. Thus, antisense RNA permits studies of gene activity in nematodes that lack extensive genetics.

David H Lum et al. (2001) International C. elegans Meeting "The intracellular domain of the feminizing receptor TRA-2A interacts directly with the transcription factor TRA-1A."

David H Lum, David Zarkower, Patricia E Kuwabara, Andrew M Spence

[International C. elegans Meeting, 2001]

In XX animals the tra-2 gene negatively regulates the activity of the three fem genes. The absence of fem activity in XX animals frees tra-1 , the terminal regulator of somatic sex determination, to promote female development. The tra-2 gene encodes two proteins TRA-2A and TRA-2B. The larger of the two proteins, TRA-2A, is a predicted transmembrane protein with a large C-terminal intracellular domain. TRA-2B is expressed in the hermaphrodite germline and is predicted to be a soluble protein consisting of just the C-terminal domain of TRA-2A. The intracellular domain of TRA-2A negatively regulates the FEMs through a direct interaction with FEM-3. Overexpression of the C-terminal domain of TRA-2A (TRA-2c) is sufficient for the negative regulation of FEM activity and the transformation of XO animals into females. To investigate the mechanism of TRA-2c feminizing activity we overexpressed various TRA-2c fragments. Surprisingly, a C-terminal fragment of TRA-2c (TRA-2c delta 5), incapable of interacting with FEM-3 in the yeast 2-hybrid system, maintained weak feminizing activity. Both yeast 2-hybrid and biochemical data demonstrate that TRA-2c delta 5 physically interacts with TRA-1A. tra-2(mx) mutations affect tra-2 activity in both the soma and germline. Three mx mutations all disrupt the TRA-2c/TRA-1A interaction in vitro and reduce or eliminate the feminizing activity of TRA-2c delta 5 in overexpression assays in vivo . We predicted that mutations in tra-1 that disrupt the TRA-1/TRA-2 interaction should have a phenotype similar to tra-2(mx) alleles. Several alleles of tra-1 have a smg -sensitive germline phenotype similar to that of the tra-2(mx) alleles. We found that mutations corresponding to three of the smg -sensitive tra-1 alleles lie within the TRA-2 binding domain. Two of the tra-1 alleles carry missense mutations of which one disrupts the TRA-2/TRA-1 interaction in vitro . A third tra-1 allele possesses a nonsense mutation that truncates TRA-1 leaving ten amino acids of the minimal TRA-2 binding domain. Like the tra-2(mx) mutations the tra-1 smg -sensitive mutations are predicted to disrupt the TRA-2/TRA-1 interaction in vivo . Our surprising results suggest that in both the germline and soma TRA-2 plays a role in regulating TRA-1A through a direct interaction. TRA-1A has been demonstrated to directly regulate transcription of several genes and is predicted to be nuclear localized. We observe strong nuclear localization of both GFP::TRA-1A and Myc::TRA-1A in transgenic animals. Consistent with a nuclear role for TRA-2 regulation of TRA-1A, we observe nuclear localization of a highly active GFP::TRA-2c fusion protein. Our data raise the intriguing possibility that in the soma TRA-2A is cleaved to allow the intracellular domain to enter the nucleus and interact with TRA-1A.