Friday, Andrew J. et al. (2011) International Worm Meeting "IFE-1: A Key Regulator of Germ Cell Protein Synthesis."

Friday, Andrew J., Keiper, Brett D., Henderson, Melissa A., Subash, Jacob

[International Worm Meeting, 2011]

Gamete development is governed largely by regulated translation initiation on stored mRNAs. The rate limiting step is their recruitment by translation initiation factors (eIF's) to polyribosomes. eIF4E isoforms are the first translation factors to interact with mRNAs, specifically recognizing their methylated guanosine cap structures. Our lab has shown that three of the five C. elegans eIF4E isoforms (IFE-1-5) recruit unique subsets of mRNAs. Consequently, individual IFE gene knockouts result in unique phenotypes in the soma and/or germ line. IFE-1 is the only isoform found in P-granules and associated with PGL-1 in the germ line. Loss of IFE-1 causes temperature-sensitive sterility due to defective cytokinesis in secondary spermatocytes as well as diminished oogenesis and reduced viability of oocytes. Reintroduction of flag-tagged IFE-1 into the ife-1(bn127) null mutants caused a partial recovery of fertility and gametogenesis phenotypes. In order to further understand the mechanistic role of IFE-1 in mRNA translation during oocyte and spermatocyte development, polysomal microarray analyses were performed to identify the unique set of mRNAs recruited by IFE-1. Current evidence suggests that key post-meiotic steps in gametogenesis are regulated by IFE-1 action on a specific subset of mRNAs.

Fire A et al. (1994) Worm Breeder's Gazette "Vectorology I: New lacZ Vectors (Building a Better Gene Trap)."

Fire A, Xu SQ

[Worm Breeder's Gazette, 1994]

Vectorology I: New lacZ vectors ("building a better gene trap") Andrew Fire and SiQun Xu Carnegie Institution of Washington, Baltimore, Md 21210

Mehra A et al. (1994) Worm Breeder's Gazette "Direct Interaction Between FEM-3 and a Carboxy-Terminal Fragment of TRA-2A"

Spence AM, Heck L, Kuwabara PE, Mehra A

[Worm Breeder's Gazette, 1994]

Direct Interaction between FEM-3 and a Carboxy-Terminal Fragment Or TRA-2A Arun Mehra, Linda Heck, Patricia Kuwabara*, and Andrew Spence Dept. of Medical Genetics, University of Toronto, 1 King's College Circle, Toronto, Canada, and *MRC Laboratory of Molecular Biology, Hills Rd., Cambridge, UK

McGhee JD (1987) Biochemistry "Purification and characterization of a carboxylesterase from the intestine of the nematode Caenorhabditis elegans."

McGhee JD

[Biochemistry, 1987]

The major intestinal esterase from the nematode Caenorhabditis elegans has been purified to essential homogeneity. Starting from whole worms, the overall purification is 9000-fold with a 10% recovery of activity. The esterase is a single polypeptide chain of Mr 60,000 and is stoichiometrically inhibited by organophosphates. Substrate preferences and inhibition patterns classify the enzyme as a carboxylesterase (EC 3.1.1.1), but the physiological function is unknown. The sequence of 13 amino acid residues at the esterase N- terminus has been determined. This partial sequence shows a surprisingly high degree of similarity to the N-terminal sequence of two carboxylesterases recently isolated from Drosophila mojavensis [Pen, J., van Beeumen, J., & Beintema, J. J. (1986) Biochem. J. 238, 691-699].

Wendy Wong et al. (2006) European Worm Meeting "The Integrative Interaction Map for Caenorhabditis elegans"

Wendy Wong, Andrew Fraser

[European Worm Meeting, 2006]

. Wendy Wong and Andrew Fraser. C. elegans is a popular model system for the systematic analysis. However, relatively little is known for its networks of genetic interactions. We hereby construct an integrative interaction map for C. elegans by integrating diverse functional genomics Datasets. We will also present some of the novel tools in querying the interaction map for answering powerful biological hypotheses.

Huggins, Hayden P. et al. (2017) International Worm Meeting "Cap-dependent protein synthesis is critical for embryonic development in C. elegans."

Huggins, Hayden P., Keiper , Brett D., Hoffman , Jenna L., Friday , Andrew J.

[International Worm Meeting, 2017]

When and where specific proteins are synthesized is critical for determining cell identity and fate. Salient examples of this occur during gametogenesis and early embryogenesis in metazoans. Selective mRNA translational control and targeted protein turnover are cell-determining processes that generate an embryo from a fertilized egg. Yet, we know very little of how protein synthesis and turnover act in tandem in the early embryo to establish proper development. Here, we address translationally regulated mRNAs that may link synthesis and turnover between the oocyte and early blastula stages. Translation initiation comes in two flavors - one requires the mRNA cap binding protein eIF4E (cap-dependent), and one does not (cap-independent). Both begin by recruiting mRNAs to the scaffold protein eIF4G, and then to ribosomes. Some mRNAs translate more efficiently in a cap-dependent state, whereas others are efficiently translated in a cap-independent state. We previously showed that cap-independent translation increases germ cell apoptosis in vivo. Here, we show that cap-independent mRNA initiation also caused marked aberrancies in embryonic development. Remarkably, C. elegans embryos genetically depleted of cap-dependent protein synthesis completed early cleavage events, but arrested prior to elongation. This suggests that embryonic mitoses do not require cap-initiated translation. However, arrested embryos were rounded and showed an increased frequency of germ mRNPs called P granules in somatic blastulae. We are currently characterizing mRNAs/proteins associated with eIF4G and eIF4E complexes, to evaluate overlap with P granules and other germ mRNPs. We assessed the translational status of all mRNAs in nematodes with normal and depleted cap-dependent translation by polysome RNA-Seq. We identified 144 mRNAs that depend on cap-mediated translation, and 55 mRNAs that have enhanced translation when the cap-independent mechanism predominates. Interestingly, several of these genes are implicated in autophagy (e.g., atg-13, epg-2, and epg-4) and polarity establishment (e.g., ooc-3, par-2 and par-4). These cap-dependent mRNAs may be responsible for the phenotypes we observe. Our findings suggest that the balance of translation initiation mechanisms determines the spatiotemporal synthesis of lineage proteins and promotes somatic identity during embryogenesis in C. elegans.

Murakami S et al. (1999) Curr Biol "Life extension and stress resistance in Caenorhabditis elegans modulated by the tkr-1 gene."

Johnson TE, Murakami S

[Curr Biol, 1999]

In this Brief Communication, which appeared in the 14 September 1998 issue of Current Biology, the UV dose was reported erroneously. The dose reported was 20 J/m2 but the actual dose used was 0.4 J/cm2. Also, the gene formally referred to as tkr-1 has since been renamed old-1 (overexpression longevity determination).

Ramos CG et al. (2014) J Bacteriol "Retraction for Ramos et al., MtvR is a global small noncoding regulatory RNA in Burkholderia cenocepacia."

Feliciano JR, da Costa PJ, Ramos CG, Grilo AM, Leitao JH

[J Bacteriol, 2014]

Volume 195, no. 16, p. 35143523, 2013. A number of problems related to images published in this paper have been brought to our attention. Figure 1D contains duplicated images in lanes S and LE, and Fig. 4D and 6B contain images previously published in articles in this journal and in Microbiology and Microbial Pathogenesis, i.e., the following: C. G. Ramos, S. A. Sousa, A. M. Grilo, J. R. Feliciano, and J. H. Leitao, J. Bacteriol. 193:15151526, 2011. doi:10.1128/JB.01374-11. S. A. Sousa, C. G. Ramos, L. M. Moreira, and J. H. Leitao, Microbiology 156:896908, 2010. doi:10.1099/mic.0.035139-0. C. G. Ramos, S. A. Sousa, A. M. Grilo, L. Eberl, and J. H. Leitao, Microb. Pathog. 48:168177, 2010. doi: 10.1016/j.micpath.2010.02.006. Therefore, we retract the paper. We deeply regret this situation and apologize for any inconvenience to the editors and readers of Journal of Bacteriology, Microbial Pathogenesis, and Microbiology.

Nillegoda NB et al. (2015) Nature "Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation."

Berynskyy M, Morimoto RI, Bukau B, Stengel F, Kirstein J, Szlachcic A, Arnsburg K, Stank A, Scior A, Nillegoda NB, Gao X, Guilbride DL, Aebersold R, Wade RC, Mayer MP

[Nature, 2015]

Protein aggregates are the hallmark of stressed and ageing cells, and characterize several pathophysiological states. Healthy metazoan cells effectively eliminate intracellular protein aggregates, indicating that efficient disaggregation and/or degradation mechanisms exist. However, metazoans lack the key heat-shock protein disaggregase HSP100 of non-metazoan HSP70-dependent protein disaggregation systems, and the human HSP70 system alone, even with the crucial HSP110 nucleotide exchange factor, has poor disaggregation activity in vitro. This unresolved conundrum is central to protein quality control biology. Here we show that synergic cooperation between complexed J-protein co-chaperones of classes A and B unleashes highly efficient protein disaggregation activity in human and nematode HSP70 systems. Metazoan mixed-class J-protein complexes are transient, involve complementary charged regions conserved in the J-domains and carboxy-terminal domains of each J-protein class, and are flexible with respect to subunit composition. Complex formation allows J-proteins to initiate transient higher order chaperone structures involving HSP70 and interacting nucleotide exchange factors. A network of cooperative class A and B J-protein interactions therefore provides the metazoan HSP70 machinery with powerful, flexible, and finely regulatable disaggregase activity and a further level of regulation crucial for cellular protein quality control.

Miller DM et al. (1992) Worm Breeder's Gazette "unc-4 LacZ Expression in A-Type Motor Neurons"

Miller DM, Niemeyer CJ

[Worm Breeder's Gazette, 1992]

unc-4 LacZ expression in A-type motor neurons David M. Miller and Charles J. Niemeyer, Dept. of Cell Biology, Duke Univ. Medical Ctr, Durham, NC 27710