IMG [AS-SIG/Image]

About the Workshop

The organizers of AS-SIG would like to invite you to participate in the 4th Special Interest Group meeting on Alternative Splicing (AS-SIG), on July 19-20, 2007 at Vienna, Austria. This workshop is scheduled immediately before ISMB/ECCB2007 July 21-25 2007, our co-sponsor, and is jointly organized and co-sponsored by EURASNET, the new European Commission funded Network of Excellence (NoE). AS-SIG 2007 follows on from initial and subsequent successful Alternative Splicing SIG meetings held at the Pacific Symposium of Biocomputing, 2004 and the ISMB in 2005 and 2006, respectively.

Background and Aims

The control of gene expression is ubiquitous and implicated in almost every process in the cell, ranging from the fertilization of germ cells, across the cell cycle up to apoptosis. Accordingly, in order to control the expression of genes under such diverse contexts, this is exerted on different several cellular levels. Genetic regulation of gene expression involves a series of complex biochemical mechanisms, and at the level of RNA processing it involves the splicing of pre-mRNAs and subsequent mRNA nuclear-to-cytoplasmic transport, by utilization of splicing-specific signals and transport factors. In higher metazoan genomes, most protein-coding genes are transcribed as pre-mRNAs that are composed of several exons, separated by intervening regions (introns). The processing of precursors to mature mRNAs (pre-mRNA splicing) constitutes a critical mode for the regulation of gene expression. This process is accomplished in the nucleus by the spliceosome, a large RNP complex that involves five snRNAs functioning as RNPs and potentially hundreds of proteins, the core components of which are highly conserved across eukaryotic genomes. The selection of splice-sites is frequently not constitutive but variable, as additional splice sites may be used as alternatives, giving rise to multiple mRNA products and, consequently, different protein isoforms with different biochemical and/or physical properties. Splicing is a highly regulated mechanism, requiring the precise recognition of canonical splicing signals and additional splicing cis-regulatory elements to remove the introns and produce the correct message. Furthermore, the spliceosome can regulate gene expression and produce isoforms specific to different cell or tissue types, as well as to different stages of cell differentiation or development, and integrate RNA splicing with other components of RNA processing and quality control pathways. Moreover, alternative splicing also plays a crucial role in many cellular processes, including sex-determination and apoptosis; and a variation in either cis-acting elements or trans-acting factors can lead to aberrant splicing and cause a disease state. A picture emerges in which the control of gene expression is thought of as a complex network of interactions at the level of transcription, as well as at the levels of RNA processing, export and surveillance. Alternative splicing (AS) is positioned at the interplay of genomes, regulatory networks and evolution, and it has emerged as a ubiquitous and dynamic mechanism of gene regulation. This is supported by a stream of new insights and discoveries derived from the fields of genomics, bioinformatics and molecular biology, as well as new approaches toward more parallel measurements of expressed isoforms across cell types and tissues. Identifying, quantifying, analyzing and understanding the regulation, function and evolution of AS constitutes a decisive part of a Human Transcriptome Project, to eventually arrive at a cis-regulatory map of AS in model organisms. This will require close collaboration between computational and experimentally-inclined researchers, enabling us to build a community of shared tools, databases, nomenclature and standards that permit everyone to contribute what they do best, while benefiting from what everyone else has done. AS-SIG meetings aim to establish a permanent forum for computational-inclined biologists and computational biologists to discuss collaboratively, focusing on questions that demand collaborative inputs. The AS-SIG will address latest results and questions in this exciting field, and bring together bioinformatics and biology. In addition to oral presentations and a poster session, the Meeting will feature a panel discussion, which was successfully run at last year Meeting. The AS-SIG meeting will include studies of AS in both in humans and model organisms, reflecting the added biological value of comparative genomics. With the location of ISMB/ECCB 2007 in Europe, this provides an excellent condition for a joint meeting with the newly formed EURASNET.

Session topics

Session 1, Experimental and bioinformatics methodologies for alternative splicing
Experimental methods, RT-PCR-based screens; minigene systems; RNA interference-mediated screens; splicing-sensitive DNA microarrays, cross-linking and immunoprecipitation (CLIP-) based screens; small molecule approaches.
AS information and databases, transcript repositories; standards for annotating primary transcript structures; data exchange formats; structure of AS information, ontologies, abstract representations of AS events.
Algorithms and genome analyses, spliced-alignments; new tools for data-mining, computational analysis of AS events, types and rates, AS gene products and functional impact; comparative genomics and evolution of introns and AS.

Session 2, Biology of regulatory mechanisms of alternative splicing
Regulatory mechanisms of splicing, functional nucleotide sequences as cis-regulatory elements; splicing-regulatory SR proteins and hnRNPs; methods to infer novel splicing regulators; NMD as a surveillance (quality control) pathways linked to AS.
Biological function, impact of splice variants on protein structure and biological pathways; relation of pre-mRNA splicing with other mechanism of gene expression; differentiation of AS regulation and functional impact between model organisms.

Session 3, Aberrant splicing, human disease, and concepts for medical treatment
Disease biomarkers, Identification and characterization of splicing mutations and variations linked to human disease; classification of AS forms based on disease progression; diagnostic tools related to AS pattern variation linked to disease.
Medical applications, therapeutic strategies related to splicing variations between normal and diseases states; correction of disease-associated splicing defects; splicing regulators as drug targets.

Poster session