4.4 Article

Comparison of splice sites reveals that long noncoding RNAs are evolutionarily well conserved

Journal

RNA
Volume 21, Issue 5, Pages 801-812

Publisher

COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1261/rna.046342.114

Keywords

long noncoding RNAs; IncRNA; splice sites; multiple sequence alignments; evolution; conservation; evolutionary plasticity

Funding

  1. European Union FP-7 project QUANTOMICS [222664]
  2. International Cancer Genome Consortium (ICGC) - German Federal Ministry of Education and Research
  3. State of Saxony
  4. European Union

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Large-scale RNA sequencing has revealed a large number of long mRNA-like transcripts (lncRNAs) that do not code for proteins. The evolutionary history of these lncRNAs has been notoriously hard to study systematically due to their low level of sequence conservation that precludes comprehensive homology-based surveys and makes them nearly impossible to align. An increasing number of special cases, however, has been shown to be at least as old as the vertebrate lineage. Here we use the conservation of splice sites to trace the evolution of lncRNAs. We show that >85% of the human GENCODE lncRNAs were already present at the divergence of placental mammals and many hundreds of these RNAs date back even further. Nevertheless, we observe a fast turnover of intron/exon structures. We conclude that lncRNA genes are evolutionary ancient components of vertebrate genomes that show an unexpected and unprecedented evolutionary plasticity. We offer a public web service (http://splicemap.bioinf.unileipzig.de) that allows to retrieve sets of orthologous splice sites and to produce overview maps of evolutionarily conserved splice sites for visualization and further analysis.

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