Martin Ringwald

The Gene Ontology (GO) project (http://www. geneontology.org/) provides structured, controlled vocabularies and classifications that cover several domains of molecular and cellular biology and are freely available for community use in the annotation of genes, gene products and sequences. Many model organism databases and genome annotation groups use the GO and contribute their annotation sets to the GO resource. The GO database integrates the vocabularies and contributed annotations and provides full access to this information in several formats. Members of the GO Consortium continually work collectively, involving outside experts as needed, to expand and update the GO vocabularies. The GO Web resource also provides access to extensive documentation about the GO project and links to applications that use GO data for functional analyses.

Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.

The exponential growth in the volume of accessible biological information has generated a confusion of voices surrounding the annotation of molecular information about genes and their products. The Gene Ontology (GO) project seeks to provide a set of structured vocabularies for specific biological domains that can be used to describe gene products in any organism. This work includes building three extensive ontologies to describe molecular function, biological process, and cellular component, and providing a community database resource that supports the use of these ontologies. The GO Consortium was initiated by scientists associated with three model organism databases: SGD, the Saccharomyces Genome database; FlyBase, the Drosophila genome database; and MGD/GXD, the Mouse Genome Informatics databases. Additional model organism database groups are joining the project. Each of these model organism information systems is annotating genes and gene products using GO vocabulary terms and incorporating these annotations into their respective model organism databases. Each database contributes its annotation files to a shared GO data resource accessible to the public at http://www.geneontology.org/. The GO site can be used by the community both to recover the GO vocabularies and to access the annotated gene product data sets from the model organism databases. The GO Consortium supports the development of the GO database resource and provides tools enabling curators and researchers to query and manipulate the vocabularies. We believe that the shared development of this molecular annotation resource will contribute to the unification of biological information.

We have recently found that the cytoplasmic region of the cell adhesion molecule uvomorulin associates with three proteins named catenin alpha, beta, and gamma. Here we show by analysis of various mutant uvomorulin polypeptides expressed in mouse L cells that this association is mediated by a specific domain in the cytoplasmic region. A specific recognition site for catenins is located in a 72-amino acid domain. Interestingly, 69 of the 72 amino acid residues are encoded by a single exon of the uvomorulin gene. To demonstrate the direct interaction between catenins and the 72-amino acid domain, cDNA constructs composed of H-2Kd cDNA and various 3' sequences of uvomorulin were expressed in L cells. Chimeric proteins between H-2Kd and the 72-amino acid domain of uvomorulin were shown, by immunoprecipitation with anti-H-2Kd antibodies, to complex with catenin alpha, beta, and gamma. Catenins connect uvomorulin to cytoskeletal structures. We provide biochemical evidence for an association of the uvomorulin-catenin complex with actin bundles. Our results suggest that catenin alpha plays a key role in the association with actin filaments, whereas catenin beta binds more directly to the cytoplasmic region of uvomorulin. In cell aggregation assays with transfected cells expressing normal or mutant uvomorulin, the adhesive function was expressed only when uvomorulin was associated with catenins. From these results we conclude that the cytoplasmic anchorage of uvomorulin is of major biological importance.