Evolution of the unspliced transcriptome.
BACKGROUND
Despite their abundance, unspliced EST data have received little attention as a source of information on non-coding RNAs. Very little is know, therefore, about the genomic distribution of unspliced non-coding transcripts and their relationship with the much better studied regularly spliced products. In particular, their evolution has remained virtually unstudied.


RESULTS
We systematically study the evidence on unspliced transcripts available in EST annotation tracks for human and mouse, comprising 104,980 and 66,109 unspliced EST clusters, respectively. Roughly one third of these are located totally inside introns of known genes (TINs) and another third overlaps exonic regions (PINs). Eleven percent are "intergenic", far away from any annotated gene. Direct evidence for the independent transcription of many PINs and TINs is obtained from CAGE tag and chromatin data. We predict more than 2000 3'UTR-associated RNA candidates for each human and mouse. Fifteen to twenty percent of the unspliced EST cluster are conserved between human and mouse. With the exception of TINs, the sequences of unspliced EST clusters evolve significantly slower than genomic background. Furthermore, like spliced lincRNAs, they show highly tissue-specific expression patterns.


CONCLUSIONS
Unspliced long non-coding RNAs are an important, rapidly evolving, component of mammalian transcriptomes. Their analysis is complicated by their preferential association with complex transcribed loci that usually also harbor a plethora of spliced transcripts. Unspliced EST data, although typically disregarded in transcriptome analysis, can be used to gain insights into this rarely investigated transcriptome component. The frequently postulated connection between lack of splicing and nuclear retention and the surprising overlap of chromatin-associated transcripts suggests that this class of transcripts might be involved in chromatin organization and possibly other mechanisms of epigenetic control.
Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, Haertelstraße 16-18, Leipzig, D-04107, Germany. jane@bioinf.uni-leipzig.de.
Jan
J
Engelhardt
Bioinformatics Group, Department of Computer Science, and Interdisciplinary Center for Bioinformatics, University of Leipzig, Haertelstraße 16-18, Leipzig, D-04107, Germany. studla@bioinf.uni-leipzig.de.|Max Planck Institute for Mathematics in the Sciences, Inselstraße 22, Leipzig, D-04103, Germany. studla@bioinf.uni-leipzig.de.|Fraunhofer Institut for Cell Therapy and Immunology, Perlickstraße 1, Leipzig, D-04103, Germany. studla@bioinf.uni-leipzig.de.|Institute for Theoretical Chemistry, University of Vienna, Währingerstrasse 17, Vienna, A-1090, Austria. studla@bioinf.uni-leipzig.de.|Center for non-coding RNA in Technology and Health, University of Copenhagen, Grønnegårdsvej 3, Frederiksberg, 1870, Denmark. studla@bioinf.uni-leipzig.de.|Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, 87501, NM, USA. studla@bioinf.uni-leipzig.de.
Peter F
PF
Stadler
D000818:Animals; D005075:Biological Evolution; D002843:Chromatin; D005091:Exons; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D016678:Genome; D015894:Genome, Human; D006801:Humans; D007438:Introns; D051379:Mice; D058977:Molecular Sequence Annotation; D012326:RNA Splicing; D062085:RNA, Long Noncoding / Q000235:genetics; D059467:Transcriptome; D020506:Untranslated Regions
D002843:Chromatin; D062085:RNA, Long Noncoding; D020506:Untranslated Regions