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Characterisation of a novel minisatellite that provides multiple splice donor sites in an interferon-induced transcript.

ABSTRACT: Nucleotide sequence features of the human interferon-inducible gene 6-16 are described and include, within a CpG island, a partially expressed minisatellite consisting of 26 tandemly repeated dodecanucleotides. The repeat unit consensus sequence (CAGGTAAGGGTG) is similar to the mammalian splice donor consensus sequence [(A/C)AGGT(A/G)AGT]. The splice donor site of exon 2, as determined previously, forms part of the most upstream of the repeat units. We show that the two neighbouring repeat units also provide functional splice donor sites effectively extending exon 2 by 12 or 24 nt and inserting four or eight amino acids respectively into the predicted gene product. A similar pattern of differently spliced transcripts is detected in several human cell types. Both the number of repeat units per allele and the nucleotide sequence itself show limited polymorphism within the human population. Similar minisatellites from nonhuman primates are described and also appear to modulate splicing of a 6-16 transcript. The 6-16 minisatellite is therefore an example of tandemly repeated DNA that has a role in gene expression and may provide a useful in vivo system for the analysis of 5' splice site choice and minisatellite biology.

SUBMITTER: Turri MG

PROVIDER: S-EPMC306954 | biostudies-other | 1995 Jun

REPOSITORIES: biostudies-other

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Characterisation of a novel minisatellite that provides multiple splice donor sites in an interferon-induced transcript.

Turri M G MG Cuin K A KA Porter A C AC

Nucleic acids research 19950601 11

Nucleotide sequence features of the human interferon-inducible gene 6-16 are described and include, within a CpG island, a partially expressed minisatellite consisting of 26 tandemly repeated dodecanucleotides. The repeat unit consensus sequence (CAGGTAAGGGTG) is similar to the mammalian splice donor consensus sequence [(A/C)AGGT(A/G)AGT]. The splice donor site of exon 2, as determined previously, forms part of the most upstream of the repeat units. We show that the two neighbouring repeat units ...[more]

PMID: 7596809

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Project description:Type III interferons (IFNLs) have critical roles in the host's innate immune system, also serving as the first line against pathogenic infections of mucosal surfaces. In mammals, several IFNLs have been reported; however, only limited data on the repertoire of IFNLs in avian species is available. Previous studies showed only one member in chicken (chIFNL3). Herein, we identified a novel chicken IFNL for the first time, termed chIFNL3a, which contains 354 bp, and encodes 118 amino acids. The predicted protein is 57.1% amino acid identity with chIFNL. Genetic, evolutionary, and sequence analyses indicated that the new open reading frame (ORF) groups with type III chicken IFNs represent a novel splice variant. Compared to IFNs from different species, the new ORF is clustered within the type III IFNs group. Further study showed that chIFNL3a could activate a panel of IFN-regulated genes and function mediated by the IFNL receptor, and chIFNL3a markedly inhibited the replication of Newcastle disease virus (NDV) and influenza virus in vitro. These data collectively shed light on the repertoire of IFNs in avian species and provide useful information that further elucidate the interaction of the chIFNLs and viral infection of poultry. IMPORTANCE Interferons (IFNs) are critical soluble factors in the immune system, and are composed of 3 types (I, II, and III) that utilize different receptor complexes (IFN-αR1/IFN-αR2, IFN-γR1/IFN-γR2, and IFN-λR1/IL-10R2, respectively). Herein, we identified IFNL from the genomic sequences of chicken and termed it chIFNL3a, located on chromosome 7 of chicken. Phylogenetically clustered with all known types of chicken IFNs, the finding of this IFN is considered a type III IFN. To further evaluate the biological properties of chIFNL3a, the target protein was prepared by the baculovirus expression system (BES), which could markedly inhibit the replication of NDV and influenza viruses. In this study, we uncovered a new interferon lambda splice variant of chicken, termed chIFNL3a, which could inhibit viral replication in cells. Importantly, these novel findings may extend to other viruses, offering a new direction for therapeutic interventions.

Project description:BackgroundSplice sites prediction has been a long-standing problem in bioinformatics. Although many computational approaches developed for splice site prediction have achieved satisfactory accuracy, further improvement in predictive accuracy is significant, for it is contributing to predict gene structure more accurately. Determining a proper window size before prediction is necessary. Overly long window size may introduce some irrelevant features, which would reduce predictive accuracy, while the use of short window size with maximum information may performs better in terms of predictive accuracy and time cost. Furthermore, the number of false splice sites following the GT-AG rule far exceeds that of true splice sites, accurate and rapid prediction of splice sites using imbalanced large samples has always been a challenge. Therefore, based on the short window size and imbalanced large samples, we developed a new computational method named chi-square decision table (χ2-DT) for donor splice site prediction.ResultsUsing a short window size of 11 bp, χ2-DT extracts the improved positional features and compositional features based on chi-square test, then introduces features one by one based on information gain, and constructs a balanced decision table aimed at implementing imbalanced pattern classification. With a 2000:271,132 (true sites:false sites) training set, χ2-DT achieves the highest independent test accuracy (93.34%) when compared with three classifiers (random forest, artificial neural network, and relaxed variable kernel density estimator) and takes a short computation time (89 s). χ2-DT also exhibits good independent test accuracy (92.40%), when validated with BG-570 mutated sequences with frameshift errors (nucleotide insertions and deletions). Moreover, χ2-DT is compared with the long-window size-based methods and the short-window size-based methods, and is found to perform better than all of them in terms of predictive accuracy.ConclusionsBased on short window size and imbalanced large samples, the proposed method not only achieves higher predictive accuracy than some existing methods, but also has high computational speed and good robustness against nucleotide insertions and deletions.ReviewersThis article was reviewed by Ryan McGinty, Ph.D. and Dirk Walther.

Dataset Information

Characterisation of a novel minisatellite that provides multiple splice donor sites in an interferon-induced transcript.

Publications

Characterisation of a novel minisatellite that provides multiple splice donor sites in an interferon-induced transcript.

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