Characteristics and regulatory elements defining constitutive splicing and different modes of alternative splicing in human and mouse

Zheng, Christina; Fu, Xiang‐Dong; Gribskov, Michael

doi:10.1261/rna.2660805

Cited by 88 publications

(78 citation statements)

References 45 publications

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“…Besides phylogenetic conservation, the strength of the splice sites and the exon/intron architecture (defined in Materials and Methods) has a high impact on the prediction quality of the code. As previously reported (Stamm et al 2000;Clark and Thanaraj 2002;Zheng et al 2005), constitutive splice sites are stronger than alternative splice sites. While constitutive exons in our data sets showed an average combined MES of both splice sites of 17.06, rarely included cassette exons only showed a combined average MES of 13.71.…”

Section: Information Gainsupporting

confidence: 81%

Splicing predictions reliably classify different types of alternative splicing

Busch

Hertel

2015

RNA

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Alternative splicing is a key player in the creation of complex mammalian transcriptomes and its misregulation is associated with many human diseases. Multiple mRNA isoforms are generated from most human genes, a process mediated by the interplay of various RNA signature elements and trans-acting factors that guide spliceosomal assembly and intron removal. Here, we introduce a splicing predictor that evaluates hundreds of RNA features simultaneously to successfully differentiate between exons that are constitutively spliced, exons that undergo alternative 5 ′ or 3 ′ splice-site selection, and alternative cassette-type exons. Surprisingly, the splicing predictor did not feature strong discriminatory contributions from binding sites for known splicing regulators. Rather, the ability of an exon to be involved in one or multiple types of alternative splicing is dictated by its immediate sequence context, mainly driven by the identity of the exon's splice sites, the conservation around them, and its exon/intron architecture. Thus, the splicing behavior of human exons can be reliably predicted based on basic RNA sequence elements.

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Section: Information Gainsupporting

confidence: 81%

Splicing predictions reliably classify different types of alternative splicing

Busch

Hertel

2015

RNA

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“…We also examined whether our results could be explained by splice site strength, which has been previously reported to be lower in minor-form exons than in majorform and constitutive exons (Itoh et al 2004;Baek and Green 2005;Zheng et al 2005). The scatterplot of maxent splice site score versus intron length (Fig.…”

Section: Analysis Of Gc Content Splice Site Strength and Intron Conmentioning

confidence: 88%

“…Upstream or downstream introns <120 nt were excluded. For each upstream or downstream intron, the first and last 50 nt were excluded, since previous studies have shown that patterns of alternative splicing can strongly affect sequence conservation in these flanking intronic regions Kaufmann et al 2004;Baek and Green 2005;Xing and Lee 2005;Zheng et al 2005;Sugnet et al 2006). The clipped intron regions were then queried against the UCSC hg17_multiz17way multigenome alignment (using the software package Pygr, http://bioinformatics.…”

Section: Data Analysesmentioning

confidence: 99%

The effect of intron length on exon creation ratios during the evolution of mammalian genomes

Roy

Kim²,

Xing³

et al. 2008

RNA

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Recent studies report that alternatively spliced exons tend to occur in longer introns, which is attributed to the length constraints for splice site pairing for the two major splicing mechanisms, intron definition versus exon definition. Using genomewide studies of EST and microarray data from human and mouse, we have analyzed the distribution of various subsets of alternatively spliced exons, based on their inclusion level and evolutionary history, versus increasing intron length. Alternative exons may be included in either a major or minor fraction of all transcripts (known as major-form and minor-form exons, respectively). We find that major-form exons are seven-to eightfold more likely to be contained in short introns (<400 nt) than minor-form exons, which occur preferentially in longer introns. Since minor-form exons are more likely to be novel (;75%), this implied that novel exons arise more frequently in longer introns. To test this hypothesis, we used whole genome alignments to classify exons according to their phylogenetic age. We find that older exons, i.e., exons that are conserved in all mammals, predominate at shorter intron lengths, for both major-and minor-form exons. In contrast, exons that arose recently during primate evolution are more prevalent at longer intron lengths (>1000 nt). This suggests that the observed correlation of longer intron lengths with alternatively spliced exons may be at least partly due to biases in the probability of exon creation, which is higher in long introns.

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“…Alternative splicing is a deviation from this preferred sequence where certain exons are skipped resulting in various forms of mature mRNA. Weaker splicing signals at alternative splice sites, shorter exon length or higher sequence conservation surrounding orthologous alternative exons influence the exons that are ultimately included in the mature mRNA (5). This process is mediated by a dynamic and flexible macromolecular machine, the spliceosome, which works in a synergistic and antistatic manner (as explained below) (6,7).…”

Section: Introductionmentioning

confidence: 99%

Mechanism of alternative splicing and its regulation

et al. 2014

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Abstract. Alternative splicing of precursor mRNA is an essential mechanism to increase the complexity of gene expression, and it plays an important role in cellular differentiation and organism development. Regulation of alternative splicing is a complicated process in which numerous interacting components are at work, including cis-acting elements and trans-acting factors, and is further guided by the functional coupling between transcription and splicing. Additional molecular features, such as chromatin structure, RNA structure and alternative transcription initiation or alternative transcription termination, collaborate with these basic components to generate the protein diversity due to alternative splicing.

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Characteristics and regulatory elements defining constitutive splicing and different modes of alternative splicing in human and mouse

Cited by 88 publications

References 45 publications

Splicing predictions reliably classify different types of alternative splicing

Splicing predictions reliably classify different types of alternative splicing

The effect of intron length on exon creation ratios during the evolution of mammalian genomes

Mechanism of alternative splicing and its regulation

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