Human-mouse comparative genomics is an informative tool to assess sequence functionality as inferred from its conservation level. We used this approach to examine dependency among different positions of the 5' splice site. We compiled a data set of 50,493 homologous human-mouse internal exons and analyzed the frequency of changes among different positions of homologous human-mouse 5' splice-sit...

Alternative splicing is regulated by splicing factors that modulate splice site selection. In some cases, however, splicing factors show antagonistic activities by either activating or repressing splicing. Here, we show that these opposing outcomes are based on their binding location relative to regulated 5' splice sites. SR proteins enhance splicing only when they are recruited to the exon. Ho...

Spliceosome formation is initiated by the recognition of the 50 splice site through formation of an RNA duplex between the 50 splice site and U1 snRNA. We have previously shown that RNA duplex formation between U1 snRNA and the 50 splice site can protect pre-mRNAs from degradation prior to splicing. This initial RNA duplex must be disrupted to expose the 50 splice site sequence for base pairing...

Abstract RNA splicing, and variations in this process referred to as alternative are critical aspects of gene regulation eukaryotes. From environmental responses plants being a primary link between genetic variation disease humans, splicing differences confer extensive phenotypic changes across diverse organisms (1–3). Regulation occurs through differential selection splice sites reaction, whic...

Many disease-causing mutations affecting donor splice site recognition are reported in the literature. One of the more frequently observed nucleotide changes causing aberrant splicing are due to mutations in the donor splice site which lower the strength of base pairing with U1 snRNA (small nuclear RNA). However, recent data have highlighted the possibility of a recognition mechanism for weak d...

In their letter Hiller et al. mention the conservation test that was performed in [1] and the more recent results of Akerman and Mandel-Gutfreund [2]. To explain our interpretation of these results we first briefly describe our rough hypothesis for the origin of the bulk of NAGNAG splice variations. We believe that in general the splicing machinery splices invariantly at the first AG that follo...

Alternative splicing (AS) modulates many physiological and pathological processes. For instance, AS of the BCL-X gene balances cell survival and apoptosis in development and cancer. Herein, we identified the polypyrimidine tract binding protein (PTBP1) as a direct regulator of BCL-X AS. Overexpression of PTBP1 promotes selection of the distal 5' splice site in BCL-X exon 2, generating the pro-a...

Pre-mRNA splicing in plants, while generally similar to the processes in vertebrates and yeast, is thought to involve plant specific cis-acting elements. Both monocot and dicot introns are typically strongly enriched in U nucleotides, and AU- or U-rich segments are thought to be involved in intron recognition, splice site selection, and splicing efficiency. We have applied logitlinear models to...