Information for the Coordinates of Exons (ICE): a human splice sites database

doi:10.1016/j.ygeno.2004.05.007

Genomics

Volume 84, Issue 4, October 2004, Pages 762-766

https://doi.org/10.1016/j.ygeno.2004.05.007 Get rights and content

Abstract

We present a comprehensive database, Information for the Coordinates of Exons (ICE), of genomic splice sites (SSs) for 10,803 human genes. ICE contains 91,846 pairs of donor acceptor sites, supported by the alignment of “full-length” human mRNAs (including transcript variants) on human genomic sequences. ICE represents the largest collection of human SSs known to date and provides a significant resource to both molecular biologists and bioinformaticians alike. A user can visualize and extract genomic sequences around SSs of the donor acceptor pairs and can also visualize the primary structure of individual genes. We list in this article the 22 most frequently found canonical and noncanonical splice sites. The top four most represented donor acceptor pairs (GT-AG, GC-AG, AT-AC, and GT-GG) accounted for 99.16% of our data set. In addition, we calculated the SS matrix models for the three most common donor acceptor pairs. The database is focused on providing SSs and surrounding sequence information, associated SS and sequence characteristics, and relation to overall transcript structure. It allows targeted search and presents evidence for the gene structure.

Section snippets

Acknowledgments

We thank the staff at National Center for Biotechnology Information's LocusLink and help desk (Kim Pruitt, Peter Cooper, Vyvy Pham, Barbara Ruef, etc.) for their patience and assistance. We also thank the reviewers for their valuable comments and suggestions.

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Cited by (26)

MCL-1V, a novel mouse antiapoptotic MCL-1 variant, generated by RNA splicing at a non-canonical splicing pair
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Citation Excerpt :
We also revealed that Mcl-1V mRNA is generated by splicing within the first coding exon of Mcl-1 gene at a non-canonical donor–acceptor pair (GG–TG). According to the Information for the Coordinates of Exons (ICE): a human splice sites database [22], the GG–TG pair is rare but is utilized for a splice site. It has been suggested that the N-terminus of MCL-1L is important for the intracellular localization and the antiapoptotic function [21].
Myeloid cell leukemia-1 (MCL-1) that belongs to BCL-2 family is essential for survival of hematopoietic stem cells. It is upregulated in various types of cancer and promotes cancer cell metastasis. It is known that human MCL-1 gene undergoes differential splicing and yields three mRNAs encoding antiapoptotic MCL-1L and proapoptotic MCL-1S and MCL-1ES. However, no MCL-1 variants have been reported in mouse cells. We report here a new splicing variant of mouse Mcl-1, Mcl-1V, that is expressed in a variety of mouse normal and tumor cell lines and tissues. Comparative sequence analysis of the full-length Mcl-1 and Mcl-1V cDNAs suggested that Mcl-1V mRNA results from splicing within the first coding exon of Mcl-1 gene at a non-canonical donor–acceptor pair. MCL-1V lacks 46 amino acid residues within the N-terminal region of MCL-1. It localizes in mitochondria and inhibits anoxia- and anticancer drug-induced apoptosis as potent as MCL-1, and decayed less rapidly than MCL-1 in the cells undergoing apoptosis. Collectively, our results show that mouse cells ubiquitously express antiapoptotic MCL-1V that may play a role in mitochondrial cell death.
MCL-1ES, a novel variant of MCL-1, associates with MCL-1L and induces mitochondrial cell death
2009, FEBS Letters
Myeloid cell leukemia-1 (MCL-1L) is a pro-survival member of the BCL-2 family that promotes cell survival. In this study, we identify a new splicing variant of human MCL-1 that encodes MCL-1ES (extra short). Sequence analysis indicates that this variant results from splicing within the first coding exon of MCL-1 at a non-canonical GC–AG donor–acceptor pair. The deduced sequence of MCL-1ES encodes a protein of 197 amino acids, and the PEST (proline, glutamic acid, serine, and threonine) motifs present in MCL-1L are absent. MCL-1ES interacts with MCL-1L and induces mitochondrial cell death, suggesting that alternative splicing of MCL-1 may control the fate of cells.
MINT-7255705, MINT-7255718, MINT-7255731, MINT-7255743:MCL1-ES (uniprotkb:Q07820-2) physically interacts (MI:0914) with MCL1-1L (uniprotkb:Q07820-1) by anti tag coimmunoprecipitation (MI:0007)
MINT-7255771:MCL1-ES (uniprotkb:Q07820-2) physically interacts (MI:0914) with Beta actin (uniprotkb:P60709) by anti tag coimmunoprecipitation (MI:0007)
MINT-7255781:MCL1-ES (uniprotkb:Q07820-2) physically interacts (MI:0914) with GAPDH (uniprotkb:P04406) by anti tag coimmunoprecipitation (MI:0007)
MINT-7255756:MCL1-ES (uniprotkb:Q07820-2) physically interacts (MI:0914) with COX IV (uniprotkb:P13073) by anti tag coimmunoprecipitation (MI:0007)
Computation of direct and inverse mutations with the SEGM web server (Stochastic Evolution of Genetic Motifs): An application to splice sites of human genome introns
2009, Computational Biology and Chemistry
We present here the SEGM web server (Stochastic Evolution of Genetic Motifs) in order to study the evolution of genetic motifs both in the direct evolutionary sense (past–present) and in the inverse evolutionary sense (present–past). The genetic motifs studied can be nucleotides, dinucleotides and trinucleotides. As an example of an application of SEGM and to understand its functionalities, we give an analysis of inverse mutations of splice sites of human genome introns. SEGM is freely accessible at http://lsiit-bioinfo.u-strasbg.fr:8080/webMathematica/SEGM/SEGM.html directly or by the web site http://dpt-info.u-strasbg.fr/~michel/. To our knowledge, this SEGM web server is to date the only computational biology software in this evolutionary approach.
De Novo ABCD1 Gene Mutation in an Indian Patient With Adrenoleukodystrophy
2008, Pediatric Neurology
Citation Excerpt :
Of the 3′ splice-site mutations, 87% involve the invariant AG dinucleotide, with an excess of mutations at position −2 in the intervening sequence [6]. Moreover, A is the preferred first nucleotide in the acceptor dinucleotide pair in splicing [7]. The present report describes an Indian patient with a 3′ splice-site mutation at the preferred first nucleotide (position −2) in the intervening sequence 4 of the ABCD1 gene.
A large number of ABCD1 gene mutations have been reported all over the world, but not previously in India. We report on the first known patient with childhood cerebral adrenoleukodystrophy and a de novo 3′ splice-site mutation in this gene. Magnetic resonance imaging of the brain revealed large, confluent, hyperintense areas in the bilateral cerebral white matter, predominantly parieto-occipital, with extensions into posterior regions that led to breakdown of the blood-brain barrier. An increased level of very long chain fatty acids was also consistent with the biochemical defect for adrenoleukodystrophy. Sequencing of the ABCD1 gene of this patient identified a 3′ splice-site mutation in the intervening sequence 4 (−2a > g). We did not find any mutation in the gene of the proband's mother, which confirms its de novo occurrence.
Reverse transcriptase template switching and false alternative transcripts
2006, Genomics
Reverse transcriptase (RT) can switch from one template to another in a homology-dependent manner. In the study of eukaryotic transcripts, this propensity of RT can produce an artificially deleted cDNA, which can be wrongly interpreted as an alternative transcript. Here, we have investigated the presence of such template-switching artifacts in cDNA databases, by scanning a collection of human splice sites (Information for the Coordinates of Exons, ICE database). We have confirmed several cases at the experimental level. Artifacts represent a significant portion of apparently spliced sequences using noncanonical splice signals but are rare in the context of the whole database. However, care should be taken in the annotation of alternative transcripts, especially when the RT used is poorly thermostable and when the putative intron is flanked by direct repeats, which are the substrate for template switching.
Characterization of a half-size ATP-binding cassette transporter gene which may be a useful marker for ivermectin selection in Onchocerca volvulus
2006, Molecular and Biochemical Parasitology
ATP-binding cassette (ABC) transporters comprise a large paralogous protein family and several confer drug resistance. Ivermectin (IVM) is the only drug approved for treatment of onchocerciasis and is a substrate for some ABC transporters. Furthermore, there is accumulating evidence that IVM selects on some ABC transporter genes in Onchocerca volvulus and other parasitic nematodes. The onchocerciasis control programs rely on community based treatment with IVM each year to reduce morbidity and decrease parasite transmission. This appears to be imposing selection pressure on O. volvulus. A half-size ABC transporter cDNA has previously been reported for O. volvulus, however, the full length gene has not been previously characterized and investigated for possible selection by IVM. Genes under selection may be identified by patterns of linkage disequilibrium (LD) and a loss of genetic polymorphism at physically linked loci. Twelve genetic markers spanning the full gene were examined in O. volvulus from non-treated and IVM treated populations in Ghana. Analysis of the genomic organization of the half-size ABC transporter (OvPLP) indicates that it spans approximately 3.8 kb comprising nine exons. Worms from treated people showed a reduction in gene diversity, a loss of genetic polymorphism at several markers, a selection for specific alleles, and a reduction in the number of regions in LD; these effects were more pronounced as treatment increased. These changes suggest that IVM is imposing selection pressure on this gene. The region between transmembrane domains four and five may be a useful marker for IVM selection in O. volvulus.

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¹: These authors contributed equally to this work.

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Short CommunicationInformation for the Coordinates of Exons (ICE): a human splice sites database

Abstract

Section snippets

Acknowledgments

Alternative splicing of pre-mRNA: developmental consequences and mechanisms of regulation

Annu. Rev. Genet.

Listening to silence and understanding nonsense: exonic mutations that affect splicing

Nat. Rev. Genet.

Human GC-AG alternative intron isoforms with weak donor sites show enhanced consensus at acceptor exon positions

Nucleic Acids Res.

Categorization and characterization of transcript-confirmed constitutively and alternatively spliced introns and exons from human

Hum. Mol. Genet.

A splicing silencer that regulates smooth muscle specific alternative splicing is active in multiple cell types

Nucleic Acids Res.

PALS db: Putative Alternative Splicing database

Nucleic Acids Res.

Genome-wide detection of tissue-specific alternative splicing in the human transcriptome

Nucleic Acids Res.

ASAP: the Alternative Splicing Annotation Project

Nucleic Acids Res.

Conserved sequence elements associated with exon skipping

Nucleic Acids Res.

Alternative splicing: combinatorial output from the genome

Curr. Opin. Chem. Biol.

Splicing regulation as a potential genetic modifier

Trends Genet.

A clean data set of EST-confirmed splice sites from Homo sapiens and standards for clean-up procedures

Nucleic Acids Res.

Short Communication
Information for the Coordinates of Exons (ICE): a human splice sites database