The Coupling of Alternative Splicing and Nonsense-Mediated mRNA Decay

Most human genes exhibit alternative splicing, but not all alternatively spliced transcripts produce functional proteins. Computational and experimental results indicate that a substantial fraction of alternative splicing events in humans result in mRNA isoforms that harbor a premature termination codon (PTC). These transcripts are predicted to be degraded by the nonsense-mediated mRNA decay (NMD) pathway. One explanation for the abundance of PTC-containing isoforms is that they represent splicing errors that are identified and degraded by the NMD pathway. Another potential explanation for this startling observation is that cells may link alternative splicing and NMD to regulate the abundance of mRNA transcripts. This mechanism, which we call "Regulated Unproductive Splicing and Translation" (RUST), has been experimentally shown to regulate expression of a wide variety of genes in many organisms from yeast to human. It is frequently employed for autoregulation of proteins that affect the splicing process itself. Thus, alternative splicing and NMD act together to play an important role in regulating gene expression

An Identity Crisis in the Life Sciences

Abstract. my Grid is an e-Science project assisting life scientists to build workflows that gather and co-ordinate data from distributed, autonomous, replicated and heterogeneous resources. The provenance logs of workflow executions are recorded as RDF graphs. The log of one workflow run is used to trace the history of its execution process; however, by aggregating provenance logs of workflow reruns, or runs of different workflows, we can gather the provenance of a common data product shared in multiple derivation paths. This aggregation relies on accurate and universal identification of each data product. The nature of bioinformatics data and services, however, makes this difficult. We describe the identity problem in bioinformatics data, and present a protocol for managing identity coreferences and allocating identity to collected and computed data products. The ability to overcome this problem means that the provenance of workflows in bioinformatics and other domains can be themselves exploited to enhance the practice of e-Science.

Recent advances in biocuration: meeting report from the fifth International Biocuration Conference.

The 5th International Biocuration Conference brought together over 300 scientists to exchange on their work, as well as discuss issues relevant to the International Society for Biocuration's (ISB) mission. Recurring themes this year included the creation and promotion of gold standards, the need for more ontologies, and more formal interactions with journals. The conference is an essential part of the ISB's goal to support exchanges among members of the biocuration community. Next year's conference will be held in Cambridge, UK, from 7 to 10 April 2013. In the meanwhile, the ISB website provides information about the society's activities (http://biocurator.org), as well as related events of interest

Toward an Integrated RNA Motif Database

In this paper we present the design and implementation of an RNA structural motif database, called RmotifDB. The structural motifs stored in RmotifDB come from three sources: (1) collected manually from biomedical literature; (2) submitted by scientists around the world; and (3) discovered by a wide variety of motif mining methods. We present here a motif mining method in detail. We also describe the interface and search mechanisms provided by RmotifDB as well as techniques used to integrate RmotifDB with the Gene Ontology. The RmotifDB system is fully operational and accessible on the Internet at http://datalab.njit.edu/bioinfo