MersV1, Main, Exploration, bibRecord, 002442

Quantitative evaluation of all hexamers as exonic splicing elements.

Identifieur interne : 002442 ( Main/Exploration ); précédent : 002441; suivant : 002443

Quantitative evaluation of all hexamers as exonic splicing elements.

Auteurs : Shengdong Ke [États-Unis] ; Shulian Shang ; Sergey M. Kalachikov ; Irina Morozova ; Lin Yu ; James J. Russo ; Jingyue Ju ; Lawrence A. Chasin

Source :

Genome research [ 1549-5469 ] ; 2011.

RBID : pubmed:21659425

Descripteurs français

KwdFr :
- ARN (génétique), Chromatine (génétique), Conformation d'acide nucléique, Exons (génétique), Humains, Sites d'épissage d'ARN, Séquences régulatrices de l'acide ribonucléique, Épissage des ARN (génétique).
MESH :
- génétique : ARN, Chromatine, Exons, Épissage des ARN.
- Conformation d'acide nucléique, Humains, Sites d'épissage d'ARN, Séquences régulatrices de l'acide ribonucléique.

English descriptors

KwdEn :
- Chromatin (genetics), Exons (genetics), Humans, Nucleic Acid Conformation, RNA (genetics), RNA Splice Sites, RNA Splicing (genetics), Regulatory Sequences, Ribonucleic Acid.
MESH :
- chemical , genetics : Chromatin, RNA.
- genetics : Exons, RNA Splicing.
- Humans, Nucleic Acid Conformation, RNA Splice Sites, Regulatory Sequences, Ribonucleic Acid.

Abstract

We describe a comprehensive quantitative measure of the splicing impact of a complete set of RNA 6-mer sequences by deep sequencing successfully spliced transcripts. All 4096 6-mers were substituted at five positions within two different internal exons in a 3-exon minigene, and millions of successfully spliced transcripts were sequenced after transfection of human cells. The results allowed the assignment of a relative splicing strength score to each mutant molecule. The effect of 6-mers on splicing often depended on their location; much of this context effect could be ascribed to the creation of different overlapping sequences at each site. Taking these overlaps into account, the splicing effect of each 6-mer could be quantified, and 6-mers could be designated as enhancers (ESEseqs) and silencers (ESSseqs), with an ESRseq score indicating their strength. Some 6-mers exhibited positional bias relative to the two splice sites. The distribution and conservation of these ESRseqs in and around human exons supported their classification. Predicted RNA secondary structure effects were also seen: Effective enhancers, silencers and 3' splice sites tend to be single stranded, and effective 5' splice sites tend to be double stranded. 6-mers that may form positive or negative synergy with another were also identified. Chromatin structure may also influence the splicing enhancement observed, as a good correspondence was found between splicing performance and the predicted nucleosome occupancy scores of 6-mers. This approach may prove of general use in defining nucleic acid regulatory motifs, substitute for functional SELEX in most cases, and provide insights about splicing mechanisms.

DOI: 10.1101/gr.119628.110
PubMed: 21659425

Affiliations:

Le document en format XML

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<front><div type="abstract" xml:lang="en">We describe a comprehensive quantitative measure of the splicing impact of a complete set of RNA 6-mer sequences by deep sequencing successfully spliced transcripts. All 4096 6-mers were substituted at five positions within two different internal exons in a 3-exon minigene, and millions of successfully spliced transcripts were sequenced after transfection of human cells. The results allowed the assignment of a relative splicing strength score to each mutant molecule. The effect of 6-mers on splicing often depended on their location; much of this context effect could be ascribed to the creation of different overlapping sequences at each site. Taking these overlaps into account, the splicing effect of each 6-mer could be quantified, and 6-mers could be designated as enhancers (ESEseqs) and silencers (ESSseqs), with an ESRseq score indicating their strength. Some 6-mers exhibited positional bias relative to the two splice sites. The distribution and conservation of these ESRseqs in and around human exons supported their classification. Predicted RNA secondary structure effects were also seen: Effective enhancers, silencers and 3' splice sites tend to be single stranded, and effective 5' splice sites tend to be double stranded. 6-mers that may form positive or negative synergy with another were also identified. Chromatin structure may also influence the splicing enhancement observed, as a good correspondence was found between splicing performance and the predicted nucleosome occupancy scores of 6-mers. This approach may prove of general use in defining nucleic acid regulatory motifs, substitute for functional SELEX in most cases, and provide insights about splicing mechanisms.</div>
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Serveur d'exploration MERS

Quantitative evaluation of all hexamers as exonic splicing elements.

Quantitative evaluation of all hexamers as exonic splicing elements.

Source :

Descripteurs français

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

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