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BackgroundThe barber's pole worm, Haemonchus contortus, is one of the most economically important parasites of small ruminants worldwide. Although this parasite can be controlled using anthelmintic drugs, resistance against most drugs in common use has become a widespread problem. We provide a draft of the genome and the transcriptomes of all key developmental stages of H. contortus to support biological and biotechnological research areas of this and related parasites.ResultsThe draft genome of H. contortus is 320 Mb in size and encodes 23,610 protein-coding genes. On a fundamental level, we elucidate transcriptional alterations taking place throughout the life cycle, characterize the parasite's gene silencing machinery, and explore molecules involved in development, reproduction, host-parasite interactions, immunity, and disease. The secretome of H. contortus is particularly rich in peptidases linked to blood-feeding activity and interactions with host tissues, and a diverse array of molecules is involved in complex immune responses. On an applied level, we predict drug targets and identify vaccine molecules.ConclusionsThe draft genome and developmental transcriptome of H. contortus provide a major resource to the scientific community for a wide range of genomic, genetic, proteomic, metabolomic, evolutionary, biological, ecological, and epidemiological investigations, and a solid foundation for biotechnological outcomes, including new anthelmintics, vaccines and diagnostic tests. This first draft genome of any strongylid nematode paves the way for a rapid acceleration in our understanding of a wide range of socioeconomically important parasites of one of the largest nematode orders.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2009.01.053 Byline: Christopher M. Hammell (1), Isabella Lubin (1), Peter R. Boag (2), T. Keith Blackwell (2), Victor Ambros (1) Keywords: RNA; DEVBIO; STEMCELL Abstract: TRIM-NHL proteins represent a large class of metazoan proteins implicated in development and disease. We demonstrate that a C. elegans TRIM-NHL protein, NHL-2, functions as a cofactor for the microRNA-induced silencing complex (miRISC) and thereby enhances the posttranscriptional repression of several genetically verified microRNA targets, including hbl-1 and let-60/Ras (by the let-7 family of microRNAs) and cog-1 (by the lsy-6 microRNA). NHL-2 is localized to cytoplasmic P-bodies and physically associates with the P-body protein CGH-1 and the core miRISC components ALG-1/2 and AIN-1. nhl-2 and cgh-1 mutations compromise the repression of microRNA targets in vivo but do not affect microRNA biogenesis, indicating a role for an NHL-2:CGH-1 complex in the effector phase of miRISC activity. We propose that the NHL-2:CGH-1 complex functions in association with mature miRISC to modulate the efficacy of microRNA:target interactions in response to physiological and developmental signals, thereby ensuring the robustness of genetic regulatory pathways regulated by microRNAs. Author Affiliation: (1) Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA (2) Joslin Diabetes Center, Department of Pathology, Harvard Medical School, Harvard Stem Cell Institute, One Joslin Place, Boston, MA 02215, USA Article History: Received 28 August 2008; Revised 19 December 2008; Accepted 28 January 2009 Article Note: (miscellaneous) Published: March 5, 2009

During oogenesis, numerous messenger RNAs (mRNAs) are maintained in a translationally silenced state. In eukaryotic cells, various translation inhibition and mRNA degradation mechanisms congregate in cytoplasmic processing bodies (P bodies). The P body protein Dhh 1 inhibits translation and promotes decapping-mediated mRNA decay together with Pat1 in yeast, and has been implicated in mRNA storage in metazoan oocytes. Here, we have investigated in Caenorhabditis elegans whether Dhh 1 and Pat1 generally function together, and how they influence mRNA sequestration during oogenesis. We show that in somatic tissues, the Dhh 1 orthologue (CGH-1)forms Pat1 (patr-1)-dependent P bodies that are involved in mRNA decapping. In contrast, during oogenesis, CGH-1 forms patr-1-independent mRNA storage bodies. CGH-1 then associates with translational regulators and a specific set of maternal mRNAs, and prevents those mRNAs from being degraded. Our results identify somatic and germ cell CGH-1 functions that are distinguished by the involvement of PATR-1, and reveal that during oogenesis, numerous translationally regulated mRNAs are specifically protected by a CGH-1-dependent mechanism.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2006.12.039 Byline: Amy K. Walker, Peter R. Boag, T. Keith Blackwell Keywords: Oocyte; Germ cell; Oocyte maturation; Meiosis; C. elegans; Transcription; CTD; CTD phosphatase; FCP-1; Ubiquitylation Abstract: Developing oocytes produce materials that will support early embryonic development then cease transcription before fertilization. Later, a distinct transcription program is established in the embryo. Little is understood about how these global gene regulation transitions are effected. We have investigated in C. elegans how oocyte transcription is influenced by maturation, a process that releases meiotic arrest and prepares for fertilization. By monitoring transcription-associated phosphorylation of the RNA polymerase II (Pol II) C-terminal domain (CTD), we find that oocyte transcription shuts down independently of maturation. Surprisingly, maturation signals then induce CTD phosphorylation that is associated specifically with transcription initiation steps and accumulates to high levels when expression of the CTD phosphatase FCP-1 is inhibited. This CTD phosphorylation is also uncovered when a ubiquitylation pathway is blocked, or when maturation is stimulated precociously. CTD phosphorylation is similarly detected during embryonic mitosis, when transcription is also largely silenced. We conclude that oocyte maturation signals induce abortive transcription events in which FCP-1 may recycle phosphorylated Pol II and that analogous processes may occur during mitosis. Our findings suggest that maturation signals may initiate preparations for embryonic transcription, possibly as part of a broader program that begins the transition from maternal to zygotic gene expression. Author Affiliation: Section on Developmental and Stem Cell Biology, Joslin Diabetes Center, Department of Pathology, Harvard Medical School, Harvard Stem Cell Institute, One Joslin Place, Boston, MA 02215, USA Article History: Received 11 August 2006; Revised 9 December 2006; Accepted 19 December 2006

A demonstration is presented that the protein kinase mammalian Ste20-like kinases (MST1) mediates oxidative stress-induced cell death in primary mammalian neurons by directly activating the FOXO transcription factors. The MST-FOX signaling link is extended to nematodes.

Germ cells use both positive and negative mRNA translational control to regulate gene expression that drives their differentiation into gametes. mRNA translational control is mediated by RNA-binding proteins, miRNAs, and translation initiation factors. We have uncovered the discrete roles of two translation initiation factor eIF4E isoforms (IFE-1 and -3) that bind m7GTP mRNA caps during C. elegans germline development. IFE-3 plays important roles in germline sex determination (GSD), where it promotes oocyte cell fate and is dispensable for spermatogenesis. IFE-3 is expressed throughout the germline, localizes to germ granules but distinct from IFE-1 and PGL-1, and facilitates oocyte growth and viability. This contrasts with the robust expression of IFE-1 in spermatocytes, the isoform that resides within P granules in spermatocytes and oocytes, and promotes late spermatogenesis. Each eIF4E is localized by its cognate eIF4E binding protein (IFE-1:PGL-1 and IFE-3:IFET-1). IFE-3 and IFET-1 regulate translation of several GSD mRNAs, but not those under control of IFE-1. Distinct mutant phenotypes, in vivo localization, and differential mRNA translation suggest independent dormant and active periods for each eIF4E isoform in the germline. [ABSTRACT FROM AUTHOR]