A General Definition and Nomenclature for Alternative Splicing Events

Abstract

Understanding the molecular mechanisms responsible for the regulation of the transcriptome present in eukaryotic cells is one of the most challenging tasks in the postgenomic era. In this regard, alternative splicing (AS) is a key phenomenon contributing to the production of different mature transcripts from the same primary RNA sequence. As a plethora of different transcript forms is available in databases, a first step to uncover the biology that drives AS is to identify the different types of reflected splicing variation. In this work, we present a general definition of the AS event along with a notation system that involves the relative positions of the splice sites. This nomenclature univocally and dynamically assigns a specific ''AS code'' to every possible pattern of splicing variation. On the basis of this definition and the corresponding codes, we have developed a computational tool (AStalavista) that automatically characterizes the complete landscape of AS events in a given transcript annotation of a genome, thus providing a platform to investigate the transcriptome diversity across genes, chromosomes, and species. Our analysis reveals that a substantial part-in human more than a quarter-of the observed splicing variations are ignored in common classification pipelines. We have used AStalavista to investigate and to compare the AS landscape of different reference annotation sets in human and in other metazoan species and found that proportions of AS events change substantially depending on the annotation protocol, species-specific attributes, and coding constraints acting on the transcripts. The AStalavista system therefore provides a general framework to conduct specific studies investigating the occurrence, impact, and regulation of AS.

A Tale of Two Glutaminases: Homologous Enzymes with Distinct Roles in Tumorigenesis

“…The GAM C-terminal sequence is 'VSFYIFLS', which is encoded by intron 2-3. Given the rarity of intron inclusion as a form of alternative splicing in mammals, it remains unclear if GAM was a result of a genetic defect in the cells from which its cDNA was isolated [33].…”

Inference of Isoforms from Short Sequence Reads

“…However, these events are not adequate to describe complex AS events as more experimental knowledge has become available (Sammeth et al, 2008b). In this work, we describe isoforms or AS events in a much general way, which is referred to as a ''bit matrix'' in Sammeth et al (2008b).…”

GDNF Signaling Regulates YBX1/mRNA Interactions in Mouse Spermatogonia.

“…Alternative splicing has distinct mechanisms, each capable of producing unique proteins from single genes. There are generally thought to be five general forms of alternative splicing including intron retention, exon skipping, mutually exclusive exons and alternative acceptor or donor sites [130,131]. Through alternative splicing, multiple protein products can be produced from a single gene, and the "cellular splicing code," or what gets spliced specifically in each tissue, is in large part determined by the unique splicing machinery components present in each cellular milieu [132].…”