PFP1, a gene encoding an Epc-N domain-containing protein, is essential for pathogenicity of the barley pathogen Rhynchosporium commune.

Scald caused by Rhynchosporium commune is an important foliar disease of barley. Insertion mutagenesis of R. commune generated a nonpathogenic fungal mutant which carries the inserted plasmid in the upstream region of a gene named PFP1. The characteristic feature of the gene product is an Epc-N domain. This motif is also found in homologous proteins shown to be components of histone acetyltransferase (HAT) complexes of fungi and animals. Therefore, PFP1 is suggested to be the subunit of a HAT complex in R. commune with an essential role in the epigenetic control of fungal pathogenicity. Targeted PFP1 disruption also yielded nonpathogenic mutants which showed wild-type-like growth ex planta, except for the occurrence of hyphal swellings. Complementation of the deletion mutants with the wild-type gene reestablished pathogenicity and suppressed the hyphal swellings. However, despite wild-type-level PFP1 expression, the complementation mutants did not reach wild-type-level virulence. This indicates that the function of the protein complex and, thus, fungal virulence are influenced by a position-affected long-range control of PFP1 expression.

Automatic extraction of mutations from Medline and cross-validation with OMIM.

Mutations help us to understand the molecular origins of diseases. Researchers, therefore, both publish and seek disease-relevant mutations in public databases and in scientific literature, e.g. Medline. The retrieval tends to be time-consuming and incomplete. Automated screening of the literature is more efficient. We developed extraction methods (called MEMA) that scan Medline abstracts for mutations. MEMA identified 24,351 singleton mutations in conjunction with a HUGO gene name out of 16,728 abstracts. From a sample of 100 abstracts we estimated the recall for the identification of mutation-gene pairs to 35% at a precision of 93%. Recall for the mutation detection alone was >67% with a precision rate of >96%. This shows that our system produces reliable data. The subset consisting of protein sequence mutations (PSMs) from MEMA was compared to the entries in OMIM (20,503 entries versus 6699, respectively). We found 1826 PSM-gene pairs to be in common to both datasets (cross-validated). This is 27% of all PSM-gene pairs in OMIM and 91% of those pairs from OMIM which co-occur in at least one Medline abstract. We conclude that Medline covers a large portion of the mutations known to OMIM. Another large portion could be artificially produced mutations from mutagenesis experiments. Access to the database of extracted mutation-gene pairs is available through the web pages of the EBI (refer to http://www.ebi. ac.uk/rebholz/index.html).

Computer-assisted generation of a protein-interaction database for nuclear receptors.

With the increasing amount of biological data available, automated methods for information retrieval become necessary. We employed computer-assisted text mining to retrieve all protein-protein interactions for nuclear receptors from MEDLINE in a systematic way. A dictionary of protein names and of terms denoting interactions was generated, and trioccurrences of two protein names and one interaction term in one sentence were retrieved. Abstracts containing at least one such trioccurrence were manually checked by biologists to select the relevant interactions out of the automatically extracted data. In total, 4360 abstracts were retrieved containing data on protein interactions for nuclear receptors. The resulting database contains all reported protein interactions involving nuclear receptors from 1966 to September 2001. Remarkably, the annual increase in number of reported interactors for nuclear receptors has been following an exponential growth curve in the years 1991 to 2001. Apparent in the data set is the high complexity of protein interactions for nuclear receptors. The number of interactions correlates with the number of published papers for a given receptor, suggesting that the number of reported interactors is a reflection of the intensity of research dedicated to a given receptor. Indeed, comparison of the retrieved data to a systematic yeast two-hybrid-based interaction analysis suggests that most NRs are similar with respect to the number of interacting proteins. The data set obtained serves as a source for information on NR interactions, as well as a reference data set for the improvement of advanced text-mining methods.

DOMINO1, a member of a small plant-specific gene family, encodes a protein essential for nuclear and nucleolar functions.

Arabidopsis embryos carrying the domino1 mutation grow slowly in comparison with wild type embryos and as a consequence reach only the globular stage at desiccation. The primary defect of the mutation at the cellular level is the large size of the nucleolus that can be observed soon after fertilization in the nuclei of both the embryo and the endosperm. The ultrastructure of mutant nucleoli is drastically different from wild type and points to a fault in ribosome biogenesis. DOMINO1 encodes a protein, which belongs to a plant-specific gene family sharing a common motif of unknown function, present in the tomato DEFECTIVE CHLOROPLASTS AND LEAVES (LeDCL) protein. Using a GFP protein fusion, we show that DOMINO1 is targeted to the nucleus. We propose that inactivation of DOMINO1 has a negative effect on ribosome biogenesis and on the rate of cell division.