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. 2005 Oct 19;33(18):5904-13.
doi: 10.1093/nar/gki893. Print 2005.

A genome-wide survey demonstrates widespread non-linear mRNA in expressed sequences from multiple species

Richard J Dixon  1 , Ian C Eperon, Laurence Hall, Nilesh J Samani
Affiliations

A genome-wide survey demonstrates widespread non-linear mRNA in expressed sequences from multiple species

Richard J Dixon et al. Nucleic Acids Res. .

"V体育2025版" Abstract

We describe here the results of the first genome-wide survey of candidate exon repetition events in expressed sequences from human, mouse, rat, chicken, zebrafish and fly. Exon repetition is a rare event, reported in <10 genes, in which one or more exons is tandemly duplicated in mRNA but not in the gene. To identify candidates, we analysed database sequences for mRNA transcripts in which the order of the spliced exons does not follow the linear genomic order of the individual gene [events we term rearrangements or repetition in exon order (RREO)]. Using a computational approach, we have identified 245 genes in mammals that produce RREO events. RREO in mRNA occurs predominantly in the coding regions of genes. However, exon 1 is never involved. Analysis of the open reading frames suggests that this process may increase protein diversity and regulate protein expression via nonsense-mediated RNA decay. The sizes of the exons and introns involved around these events suggest a gene model structure that may facilitate non-linear splicing VSports手机版. These findings imply that RREO affects a significant subset of genes within a genome and suggests that non-linear information encoded within the genomes of complex organisms could contribute to phenotypic variation. .

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Figures

Figure 1
Figure 1
An illustration of the linear and non-linear genome information spaces for a hypothetical gene that contains five exons. (A) A simple cartoon of a hypothetical gene containing five exons. (B) The total genome information space for a five-exon gene. Our approach to investigate the non-linear genome information space involved creating a set of possible non-linear exon–exon junction sequences of 100 bp (dark grey and light grey genome information spaces) for each gene. The first 50 bp are derived from the 5′ exon and the last 50 bp are derived from the 3′ exon in each possible non-linear exon–exon splice combination for all Ensembl exons from each gene.
Figure 2
Figure 2
Frequency distribution of the number of non-linear ESTs detected for each of the 170 human genes. The 170 human genes that exhibit non-linear splicing in EST sequences were assessed for the number of non-linear EST sequences within dbEST, which confirm each non-linear splice event.
Figure 3
Figure 3
An analysis of a representative sample of 100 human non-linear splicing events in EST sequences. (A) Open reading frame analysis of 100 human non-linear spliced EST sequences. CDS: non-linear splice site involves only exons within the coding sequence of the gene. UTR: non-linear splice site involves exons within the untranslated region of the gene. FrameShift: the non-linear splice introduces a frame shift in the open reading frame of the sequence when compared to the reference protein sequence for the gene. Inframe: the non-linear splice conserves the open reading frame of the sequence when compared to the reference protein sequence for the gene. STOP: the non-linear splice introduces a premature stop codon in the sequence. PTC-NMD STOP: the non-linear splice introduces a premature stop codon in the sequence that is >50 nt upstream of the final exon and is therefore a candidate sequence for nonsense-mediated RNA decay. (B) Summary of the non-linear splice locations in the proteins of 100 human events. The potential protein sequence regions affected by the 100 human non-linear human events in EST sequences. Each protein sequence was divided into thirds by the number of amino acids. The locations of the non-linear splice within the open reading frame of the protein were classified as N-terminal when occurring in the first third of the protein sequence, internal when occurring in the second third and C-terminal when occurring in the last third of the protein sequence.
Figure 4
Figure 4
A summary of the tissue sources from which the non-linear spliced ESTs for 170 human genes were derived. Tissue source information was obtained from the GenBank records of the EST sequences.
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