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WIREs RNA
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Evolutionary clues in lncRNAs

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The diversity of long non‐coding RNAs (lncRNAs) in the human transcriptome is in stark contrast to the sparse exploration of their functions concomitant with their conservation and evolution. The pervasive transcription of the largely non‐coding human genome makes the evolutionary age and conservation patterns of lncRNAs to a topic of interest. Yet it is a fairly unexplored field and not that easy to determine as for protein‐coding genes. Although there are a few experimentally studied cases, which are conserved at the sequence level, most lncRNAs exhibit weak or untraceable primary sequence conservation. Recent studies shed light on the interspecies conservation of secondary structures among lncRNA homologs by using diverse computational methods. This highlights the importance of structure on functionality of lncRNAs as opposed to the poor impact of primary sequence changes. Further clues in the evolution of lncRNAs are given by selective constraints on non‐coding gene structures (e.g., promoters or splice sites) as well as the conservation of prevalent spatio‐temporal expression patterns. However, a rapid evolutionary turnover is observable throughout the heterogeneous group of lncRNAs. This still gives rise to questions about its functional meaning. WIREs RNA 2017, 8:e1376. doi: 10.1002/wrna.1376 This article is categorized under: RNA Evolution and Genomics > Computational Analyses of RNA RNA Processing > Splicing Regulation/Alternative Splicing RNA Methods > RNA Analyses In Vitro and In Silico
Splice site conservation pattern of the HOTAIR transcript. The rows represent splice sites in the locus of HOTAIR. MaxEntScan scores 3 indicate that the orthologous position in the corresponding species (column) is likely to be a functional splice site. The 5′ end of the lncRNA is much less well conserved than its 3′ half. The first exon and intron (splice site in the bottom row of data) overlaps with the protein‐coding transcript HOXC11.
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Gains and losses of human lncRNAs across the vertebrates. The data comprise a filtered set of 5413 human lncRNA transcripts annotated in GENCODE v.14. A homolog of a human transcript is considered to be present in another species s, if a splice site in s is present at the exact sequence position homologous to a human splice site. Homolgous sequence position are determined from genome‐wide multiple sequence alignment, here the 46‐way vertebrate alignment provided through the UCSC genome browser. Event counts are based on the parsimony criterion: a gain event is annotated at edge before the last common ancestor of the observed occurrences, a loss is annotated a the edge before a maximal subtree without occurrences that is located after the gain event. (Reprinted with permission from Ref Copyright 2015 RNA Society Publication).
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Conservation pattern of amniote vault RNAs. The very uneven conservation pattern, here a well‐conserved stem structure at the ends and highly variable interior regions is typical of many evolutionarily conserved RNA elements. Secondary structure predictions for each sequence and the consensus structure of the alignment computed with RNAalifold are shown in ‘ViennaRNA notation’: matching pairs of parentheses denote base pairs, dot indicate unpaired bases. Bases pairs present in the consensus marked in color. Note that the consensus sequence (defined as the majority vote over an alignment column) does not fold into the consensus structure. The energy of the consensus structure (−22.32 kcal/mol) differs substantially from the average folding energy of the unconstrained sequences (− 35.84 kcal/mol). The ratio, here 0.623, serves as a statistically robust measure of structure conservation, e.g., in RNAz.
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RNA Processing > Splicing Regulation/Alternative Splicing
RNA Methods > RNA Analyses In Vitro and In Silico
RNA Evolution and Genomics > Computational Analyses of RNA

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