The Ontology for Biomedical Investigations

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource (http://obi-ontology.org) providing details on the people, policies, and issues being addressed in association with OBI. The current release of OBI is available at http://purl.obolibrary.org/obo/obi.owl.     

OTO: Ontology Term Organizer

Background

The need to create controlled vocabularies such as ontologies for knowledge organization and access has been widely recognized in various domains. Despite the indispensable need of thorough domain knowledge in ontology construction, most software tools for ontology construction are designed for knowledge engineers and not for domain experts to use. The differences in the opinions of different domain experts and in the terminology usages in source literature are rarely addressed by existing software.

Methods

OTO software was developed based on the Agile principles. Through iterations of software release and user feedback, new features are added and existing features modified to make the tool more intuitive and efficient to use for small and large data sets. The software is open source and built in Java.

Results

Ontology Term Organizer (OTO; http://biosemantics.arizona.edu/OTO/) is a user-friendly, web-based, consensus-promoting, open source application for organizing domain terms by dragging and dropping terms to appropriate locations. The application is designed for users with specific domain knowledge such as biology but not in-depth ontology construction skills. Specifically OTO can be used to establish is_a, part_of, synonym, and order relationships among terms in any domain that reflects the terminology usage in source literature and based on multiple experts’ opinions. The organized terms may be fed into formal ontologies to boost their coverage. All datasets organized on OTO are publicly available.

Conclusion

OTO has been used to organize the terms extracted from thirty volumes of Flora of North America and Flora of China combined, in addition to some smaller datasets of different taxon groups. User feedback indicates that the tool is efficient and user friendly. Being open source software, the application can be modified to fit varied term organization needs for different domains.     

Dizeez: An Online Game for Human Gene-Disease Annotation

Structured gene annotations are a foundation upon which many bioinformatics and statistical analyses are built. However the structured annotations available in public databases are a sparse representation of biological knowledge as a whole. The rate of biomedical data generation is such that centralized biocuration efforts struggle to keep up. New models for gene annotation need to be explored that expand the pace at which we are able to structure biomedical knowledge. Recently, online games have emerged as an effective way to recruit, engage and organize large numbers of volunteers to help address difficult biological challenges. For example, games have been successfully developed for protein folding (Foldit), multiple sequence alignment (Phylo) and RNA structure design (EteRNA). Here we present Dizeez, a simple online game built with the purpose of structuring knowledge of gene-disease associations. Preliminary results from game play online and at scientific conferences suggest that Dizeez is producing valid gene-disease annotations not yet present in any public database. These early results provide a basic proof of principle that online games can be successfully applied to the challenge of gene annotation. Dizeez is available at http://genegames.org.     

Functional Genomic Identification of Genes Required for Male Gonadal Differentiation in Caenorhabditis elegans

The Caenorhabditis elegans somatic gonad develops from a four-cell primordium into a mature organ that differs dramatically between the sexes in overall morphology (two arms in hermaphrodites and one in males) and in the cell types comprising it. Gonadal development in C. elegans is well studied, but regulation of sexual differentiation, especially later in gonadal development, remains poorly elucidated. To identify genes involved in this process, we performed a genome-wide RNAi screen using sex-specifically expressed gonadal GFP reporters. This screen identified several phenotypic classes, including ∼70 genes whose depletion feminized male gonadal cells. Among the genes required for male cell fate specification are Wnt/β-catenin pathway members, cell cycle regulators, and genes required for mitotic spindle function and cytokinesis. We find that a Wnt/β-catenin pathway independent of extracellular Wnt ligand is essential for asymmetric cell divisions and male differentiation during gonadal development in larvae. We also find that the cell cycle regulators cdk-1 and cyb-3 and the spindle/cytokinesis regulator zen-4 are required for Wnt/β-catenin pathway activity in the developing gonad. After sex is determined in the gonadal primordium the global sex determination pathway is dispensable for gonadal sexual fate, suggesting that male cell fates are promoted and maintained independently of the global pathway during this period.THE Caenorhabditis elegans gonad derives from a simple primordium of four cells that coalesces during embryogenesis and contains two somatic gonad precursors (SGPs), Z1 and Z4, flanking two germline precursors, Z2 and Z3 (Kimble and Hirsh 1979). The SGPs undergo very different developmental programs in each sex, involving sexually dimorphic cell lineages and migrations and sex-specific cellular differentiation. The result is a two-armed bilaterally symmetrical gonad in the adult hermaphrodite or a single-armed asymmetric gonad in the adult male. The high degree of sexual dimorphism of the mature organ and variety of cellular events that occur sex specifically during its development make the C. elegans gonad an outstanding model for sex-specific organogenesis.Development of the somatic gonad occurs in two phases. The early phase defines the gonadal axes and establishes the precursors of the major gonadal cell types. This takes place during the first larval stage (L1), beginning shortly after hatching with the first division of the SGPs. In both sexes SGP division is asymmetric in terms of both the sizes and the fates of the daughter cells, and establishes the proximal/distal axis of the gonad (Hirsh et al. 1976; Kimble and Hirsh 1979). The global sex determination pathway establishes the future sex of the gonad around the time of hatching (Klass et al. 1976; Nelson et al. 1978), and sexual dimorphism is already apparent when the SGPs divide: the size asymmetry of the SGP daughters is much more pronounced in males than hermaphrodites. In both sexes the asymmetry of the first SGP division requires a Wnt/β-catenin pathway. Mutations compromising this pathway cause a “symmetrical sisters” phenotype in which both daughters adopt the same fate (Miskowski et al. 2001; Siegfried and Kimble 2002; Phillips and Kimble 2009). Sex specificity is imposed on the SGPs by the global sex determining gene tra-1 (Hodgkin 1987) and the gonad-specific sex determining gene fkh-6 (Chang et al. 2004). These genes play opposing roles in SGP sex determination, with tra-1 feminizing and fkh-6 masculinizing the somatic gonad, and they also act redundantly to promote mitotic proliferation of the SGP lineage (Chang et al. 2004). SGP sex determination is linked to cell cycle progression by cyclin D, which is required to overcome repression of fkh-6 expression in the SGPs by E2F (Tilmann and Kimble 2005).The later phase of gonadal development involves the elongation of the gonad, together with cellular proliferation and differentiation, and lasts from L2 to adulthood. During L2 the somatic cells enlarge and leader cells (distal tip cells in the hermaphrodite, linker cell in the male) begin long-range migrations that extend the gonad. During L3, somatic gonad cell division resumes in both sexes, leading to the formation of differentiated somatic cell types by the end of L3 or beginning of L4. Gonadal morphogenesis is completed and gametogenesis begins during L4 (Kimble and Hirsh 1979).Although SGP division and much of hermaphrodite gonadal development have been well studied (Hubbard and Greenstein 2000), sexual cell fate specification in the somatic gonad is more poorly understood, particularly after the L1 stage. Despite the importance of fkh-6 in promoting male differentiation, it is expressed in males only during early L1 and null mutants have incomplete gonadal sex reversal. We have therefore performed a genome-wide RNAi screen to identify additional genes required after hatching for gonadal development in each sex. Among the advantages of this approach is the ability to identify gonadal regulators that also are essential for embryonic development. To our knowledge this is the first functional genomic study of gonadal sex differentiation.The screen identified many genes whose depletion disrupts gonadogenesis in each sex and nearly 70 genes whose depletion causes gonadal feminization in males. Prominent among this latter class were components of a Wnt/β-catenin pathway, cell cycle regulators, and genes involved in mitotic spindle function and cytokinesis. We find that Wnt/β-catenin activity continues in both sexes after SGP division and is required for male cell fate commitment in the gonad. We also find that the cyclin-dependent kinase cdk-1 and its cognate cyclin cyb-3 as well as the mitotic spindle regulator zen-4 are required for gonadal Wnt/β-catenin pathway activity, providing a potential new link between the cell cycle, asymmetric division, and sexual differentiation. The feminization caused by depletion of Wnt/β-catenin pathway components or cdk-1 is independent of the global sex determination pathway, suggesting that sexual fates in the male gonad remain plastic after the primary sex determination decision.     

A modular framework for gene set analysis integrating multilevel omics data

Modern high-throughput methods allow the investigation of biological functions across multiple ‘omics’ levels. Levels include mRNA and protein expression profiling as well as additional knowledge on, for example, DNA methylation and microRNA regulation. The reason for this interest in multi-omics is that actual cellular responses to different conditions are best explained mechanistically when taking all omics levels into account. To map gene products to their biological functions, public ontologies like Gene Ontology are commonly used. Many methods have been developed to identify terms in an ontology, overrepresented within a set of genes. However, these methods are not able to appropriately deal with any combination of several data types. Here, we propose a new method to analyse integrated data across multiple omics-levels to simultaneously assess their biological meaning. We developed a model-based Bayesian method for inferring interpretable term probabilities in a modular framework. Our Multi-level ONtology Analysis (MONA) algorithm performed significantly better than conventional analyses of individual levels and yields best results even for sophisticated models including mRNA fine-tuning by microRNAs. The MONA framework is flexible enough to allow for different underlying regulatory motifs or ontologies. It is ready-to-use for applied researchers and is available as a standalone application from http://icb.helmholtz-muenchen.de/mona.     

Predicting the spatial organization of chromosomes using epigenetic data

Chromosome folding can reinforce the demarcation between euchromatin and heterochromatin. Two new studies show how epigenetic data, including DNA methylation, can accurately predict chromosome folding in three dimensions. Such computational approaches reinforce the idea of a linkage between epigenetically marked chromatin domains and their segregation into distinct compartments at the megabase scale or topological domains at a higher resolution.Please see related articles: http://dx.doi.org/10.1186/s13059-015-0741-y and http://dx.doi.org/10.1186/s13059-015-0740-z     

Somatic Point Mutation Calling in Low Cellularity Tumors

Somatic mutation calling from next-generation sequencing data remains a challenge due to the difficulties of distinguishing true somatic events from artifacts arising from PCR, sequencing errors or mis-mapping. Tumor cellularity or purity, sub-clonality and copy number changes also confound the identification of true somatic events against a background of germline variants. We have developed a heuristic strategy and software (http://www.qcmg.org/bioinformatics/qsnp/) for somatic mutation calling in samples with low tumor content and we show the superior sensitivity and precision of our approach using a previously sequenced cell line, a series of tumor/normal admixtures, and 3,253 putative somatic SNVs verified on an orthogonal platform.     

Remodeling of the Rad51 DNA Strand-Exchange Protein by the Srs2 Helicase

Homologous recombination is associated with the dynamic assembly and disassembly of DNA–protein complexes. Assembly of a nucleoprotein filament comprising ssDNA and the RecA homolog, Rad51, is a key step required for homology search during recombination. The budding yeast Srs2 DNA translocase is known to dismantle Rad51 filament in vitro. However, there is limited evidence to support the dismantling activity of Srs2 in vivo. Here, we show that Srs2 indeed disrupts Rad51-containing complexes from chromosomes during meiosis. Overexpression of Srs2 during the meiotic prophase impairs meiotic recombination and removes Rad51 from meiotic chromosomes. This dismantling activity is specific for Rad51, as Srs2 Overexpression does not remove Dmc1 (a meiosis-specific Rad51 homolog), Rad52 (a Rad51 mediator), or replication protein A (RPA; a single-stranded DNA-binding protein). Rather, RPA replaces Rad51 under these conditions. A mutant Srs2 lacking helicase activity cannot remove Rad51 from meiotic chromosomes. Interestingly, the Rad51-binding domain of Srs2, which is critical for Rad51-dismantling activity in vitro, is not essential for this activity in vivo. Our results suggest that a precise level of Srs2, in the form of the Srs2 translocase, is required to appropriately regulate the Rad51 nucleoprotein filament dynamics during meiosis.     

Probing the Boundaries of Orthology: The Unanticipated Rapid Evolution of Drosophila centrosomin

The rapid evolution of essential developmental genes and their protein products is both intriguing and problematic. The rapid evolution of gene products with simple protein folds and a lack of well-characterized functional domains typically result in a low discovery rate of orthologous genes. Additionally, in the absence of orthologs it is difficult to study the processes and mechanisms underlying rapid evolution. In this study, we have investigated the rapid evolution of centrosomin (cnn), an essential gene encoding centrosomal protein isoforms required during syncytial development in Drosophila melanogaster. Until recently the rapid divergence of cnn made identification of orthologs difficult and questionable because Cnn violates many of the assumptions underlying models for protein evolution. To overcome these limitations, we have identified a group of insect orthologs and present conserved features likely to be required for the functions attributed to cnn in D. melanogaster. We also show that the rapid divergence of Cnn isoforms is apparently due to frequent coding sequence indels and an accelerated rate of intronic additions and eliminations. These changes appear to be buffered by multi-exon and multi-reading frame maximum potential ORFs, simple protein folds, and the splicing machinery. These buffering features also occur in other genes in Drosophila and may help prevent potentially deleterious mutations due to indels in genes with large coding exons and exon-dense regions separated by small introns. This work promises to be useful for future investigations of cnn and potentially other rapidly evolving genes and proteins.     

SeqFeatR for the Discovery of Feature-Sequence Associations

Specific selection pressures often lead to specifically mutated genomes. The open source software SeqFeatR has been developed to identify associations between mutation patterns in biological sequences and specific selection pressures (“features”). For instance, SeqFeatR has been used to discover in viral protein sequences new T cell epitopes for hosts of given HLA types. SeqFeatR supports frequentist and Bayesian methods for the discovery of statistical sequence-feature associations. Moreover, it offers novel ways to visualize results of the statistical analyses and to relate them to further properties. In this article we demonstrate various functions of SeqFeatR with real data. The most frequently used set of functions is also provided by a web server. SeqFeatR is implemented as R package and freely available from the R archive CRAN (http://cran.r-project.org/web/packages/SeqFeatR/index.html). The package includes a tutorial vignette. The software is distributed under the GNU General Public License (version 3 or later). The web server URL is https://seqfeatr.zmb.uni-due.de.     

Molecular Pathways Involved in Prostate Carcinogenesis: Insights from Public Microarray Datasets

Background

Prostate cancer is currently the most frequently diagnosed malignancy in men and the second leading cause of cancer-related deaths in industrialized countries. Worldwide, an increase in prostate cancer incidence is expected due to an increased life-expectancy, aging of the population and improved diagnosis. Although the specific underlying mechanisms of prostate carcinogenesis remain unknown, prostate cancer is thought to result from a combination of genetic and environmental factors altering key cellular processes. To elucidate these complex interactions and to contribute to the understanding of prostate cancer progression and metastasis, analysis of large scale gene expression studies using bioinformatics approaches is used to decipher regulation of core processes.

Methodology/Principal Findings

In this study, a standardized quality control procedure and statistical analysis (http://www.arrayanalysis.org/) were applied to multiple prostate cancer datasets retrieved from the ArrayExpress data repository and pathway analysis using PathVisio (http://www.pathvisio.org/) was performed. The results led to the identification of three core biological processes that are strongly affected during prostate carcinogenesis: cholesterol biosynthesis, the process of epithelial-to-mesenchymal transition and an increased metabolic activity.

Conclusions

This study illustrates how a standardized bioinformatics evaluation of existing microarray data and subsequent pathway analysis can quickly and cost-effectively provide essential information about important molecular pathways and cellular processes involved in prostate cancer development and disease progression. The presented results may assist in biomarker profiling and the development of novel treatment approaches.     

Automatic Assignment of Prokaryotic Genes to Functional Categories Using Literature Profiling

In the last years, there was an exponential increase in the number of publicly available genomes. Once finished, most genome projects lack financial support to review annotations. A few of these gene annotations are based on a combination of bioinformatics evidence, however, in most cases, annotations are based solely on sequence similarity to a previously known gene, which was most probably annotated in the same way. As a result, a large number of predicted genes remain unassigned to any functional category despite the fact that there is enough evidence in the literature to predict their function. We developed a classifier trained with term-frequency vectors automatically disclosed from text corpora of an ensemble of genes representative of each functional category of the J. Craig Venter Institute Comprehensive Microbial Resource (JCVI-CMR) ontology. The classifier achieved up to 84% precision with 68% recall (for confidence≥0.4), F-measure 0.76 (recall and precision equally weighted) in an independent set of 2,220 genes, from 13 bacterial species, previously classified by JCVI-CMR into unambiguous categories of its ontology. Finally, the classifier assigned (confidence≥0.7) to functional categories a total of 5,235 out of the ∼24 thousand genes previously in categories “Unknown function” or “Unclassified” for which there is literature in MEDLINE. Two biologists reviewed the literature of 100 of these genes, randomly picket, and assigned them to the same functional categories predicted by the automatic classifier. Our results confirmed the hypothesis that it is possible to confidently assign genes of a real world repository to functional categories, based exclusively on the automatic profiling of its associated literature. The LitProf - Gene Classifier web server is accessible at: www.cebio.org/litprofGC.     

The Jaw of the Worm: GTPase-activating Protein EAT-17 Regulates Grinder Formation in Caenorhabditis elegans

Constitutive transport of cellular materials is essential for cell survival. Although multiple small GTPase Rab proteins are required for the process, few regulators of Rabs are known. Here we report that EAT-17, a novel GTPase-activating protein (GAP), regulates RAB-6.2 function in grinder formation in Caenorhabditis elegans. We identified EAT-17 as a novel RabGAP that interacts with RAB-6.2, a protein that presumably regulates vesicle trafficking between Golgi, the endoplasmic reticulum, and plasma membrane to form a functional grinder. EAT-17 has a canonical GAP domain that is critical for its function. RNA interference against 25 confirmed and/or predicted RABs in C. elegans shows that RNAi against rab-6.2 produces a phenotype identical to eat-17. A directed yeast two-hybrid screen using EAT-17 as bait and each of the 25 RAB proteins as prey identifies RAB-6.2 as the interacting partner of EAT-17, confirming that RAB-6.2 is a specific substrate of EAT-17. Additionally, deletion mutants of rab-6.2 show grinder defects identical to those of eat-17 loss-of-function mutants, and both RAB-6.2 and EAT-17 are expressed in the terminal bulb of the pharynx where the grinder is located. Collectively, these results suggest that EAT-17 is a specific GTPase-activating protein for RAB-6.2. Based on the conserved function of Rab6 in vesicular transport, we propose that EAT-17 regulates the turnover rate of RAB-6.2 activity in cargo trafficking for grinder formation.     

Structural Integrity of Centromeric Chromatin and Faithful Chromosome Segregation Requires Pat1

The kinetochore (centromeric DNA and associated protein complex) is essential for faithful chromosome segregation and maintenance of genome stability. Here we report that an evolutionarily conserved protein Pat1 is a structural component of Saccharomyces cerevisiae kinetochore and associates with centromeres in a NDC10-dependent manner. Consistent with a role for Pat1 in kinetochore structure and function, a deletion of PAT1 results in delay in sister chromatid separation, errors in chromosome segregation, and defects in structural integrity of centromeric chromatin. Pat1 is involved in topological regulation of minichromosomes as altered patterns of DNA supercoiling were observed in pat1Δ cells. Studies with pat1 alleles uncovered an evolutionarily conserved region within the central domain of Pat1 that is required for its association with centromeres, sister chromatid separation, and faithful chromosome segregation. Taken together, our data have uncovered a novel role for Pat1 in maintaining the structural integrity of centromeric chromatin to facilitate faithful chromosome segregation and proper kinetochore function.     

Asymmetric Neuroblast Divisions Producing Apoptotic Cells Require the Cytohesin GRP-1 in Caenorhabditis elegans

Cytohesins are Arf guanine nucleotide exchange factors (GEFs) that regulate membrane trafficking and actin cytoskeletal dynamics. We report here that GRP-1, the sole Caenorhabditis elegans cytohesin, controls the asymmetric divisions of certain neuroblasts that divide to produce a larger neuronal precursor or neuron and a smaller cell fated to die. In the Q neuroblast lineage, loss of GRP-1 led to the production of daughter cells that are more similar in size and to the transformation of the normally apoptotic daughter into its sister, resulting in the production of extra neurons. Genetic interactions suggest that GRP-1 functions with the previously described Arf GAP CNT-2 and two other Arf GEFs, EFA-6 and BRIS-1, to regulate the activity of Arf GTPases. In agreement with this model, we show that GRP-1’s GEF activity, mediated by its SEC7 domain, is necessary for the posterior Q cell (Q.p) neuroblast division and that both GRP-1 and CNT-2 function in the Q.posterior Q daughter cell (Q.p) to promote its asymmetry. Although functional GFP-tagged GRP-1 proteins localized to the nucleus, the extra cell defects were rescued by targeting the Arf GEF activity of GRP-1 to the plasma membrane, suggesting that GRP-1 acts at the plasma membrane. The detection of endogenous GRP-1 protein at cytokinesis remnants, or midbodies, is consistent with GRP-1 functioning at the plasma membrane and perhaps at the cytokinetic furrow to promote the asymmetry of the divisions that require its function.     

Defining Specificity Determinants of cGMP Mediated Gustatory Sensory Transduction in Caenorhabditis elegans

Cyclic guanosine monophosphate (cGMP) is a key secondary messenger used in signal transduction in various types of sensory neurons. The importance of cGMP in the ASE gustatory receptor neurons of the nematode Caenorhabditis elegans was deduced by the observation that multiple receptor-type guanylyl cyclases (rGCs), encoded by the gcy genes, and two presently known cyclic nucleotide-gated ion channel subunits, encoded by the tax-2 and tax-4 genes, are essential for ASE-mediated gustatory behavior. We describe here specific mechanistic features of cGMP-mediated signal transduction in the ASE neurons. First, we assess the specificity of the sensory functions of individual rGC proteins. We have previously shown that multiple rGC proteins are expressed in a left/right asymmetric manner in the functionally lateralized ASE neurons and are required to sense distinct salt cues. Through domain swap experiments among three different rGC proteins, we show here that the specificity of individual rGC proteins lies in their extracellular domains and not in their intracellular, signal-transducing domains. Furthermore, we find that rGC proteins are also sufficient to confer salt sensory responses to other neurons. Both findings support the hypothesis that rGC proteins are salt receptor proteins. Second, we identify a novel, likely downstream effector of the rGC proteins in gustatory signal transduction, a previously uncharacterized cyclic nucleotide-gated (CNG) ion channel, encoded by the che-6 locus. che-6 mutants show defects in gustatory sensory transduction that are similar to defects observed in animals lacking the tax-2 and tax-4 CNG channels. In contrast, thermosensory signal transduction, which also requires tax-2 and tax-4, does not require che-6, but requires another CNG, cng-3. We propose that CHE-6 may form together with two other CNG subunits, TAX-2 and TAX-4, a gustatory neuron-specific heteromeric CNG channel complex.     

Translational Control of the Oogenic Program by Components of OMA Ribonucleoprotein Particles in Caenorhabditis elegans

The oocytes of most sexually reproducing animals arrest in meiotic prophase I. Oocyte growth, which occurs during this period of arrest, enables oocytes to acquire the cytoplasmic components needed to produce healthy progeny and to gain competence to complete meiosis. In the nematode Caenorhabditis elegans, the major sperm protein hormone promotes meiotic resumption (also called meiotic maturation) and the cytoplasmic flows that drive oocyte growth. Prior work established that two related TIS11 zinc-finger RNA-binding proteins, OMA-1 and OMA-2, are redundantly required for normal oocyte growth and meiotic maturation. We affinity purified OMA-1 and identified associated mRNAs and proteins using genome-wide expression data and mass spectrometry, respectively. As a class, mRNAs enriched in OMA-1 ribonucleoprotein particles (OMA RNPs) have reproductive functions. Several of these mRNAs were tested and found to be targets of OMA-1/2-mediated translational repression, dependent on sequences in their 3′-untranslated regions (3′-UTRs). Consistent with a major role for OMA-1 and OMA-2 in regulating translation, OMA-1-associated proteins include translational repressors and activators, and some of these proteins bind directly to OMA-1 in yeast two-hybrid assays, including OMA-2. We show that the highly conserved TRIM-NHL protein LIN-41 is an OMA-1-associated protein, which also represses the translation of several OMA-1/2 target mRNAs. In the accompanying article in this issue, we show that LIN-41 prevents meiotic maturation and promotes oocyte growth in opposition to OMA-1/2. Taken together, these data support a model in which the conserved regulators of mRNA translation LIN-41 and OMA-1/2 coordinately control oocyte growth and the proper spatial and temporal execution of the meiotic maturation decision.