Evolutionary conservation of long noncoding RNAs; sequence, structure, function

By P. Johnsson, L. Lipovich, D. Grandér, Kevin V. Morris. Biochimica et Biophysica Acta, 2013

682 citations recorded by the source corpus.

Background Recent advances in genome wide studies have revealed the abundance of long non-coding RNAs (lncRNAs) in mammalian transcriptomes. The ENCODE Consortium has elucidated the prevalence of human lncRNA genes, which are as numerous as protein-coding genes. Surprisingly, many lncRNAs do not show the same pattern of high interspecies conservation as protein-coding genes. The absence of functional studies and the frequent lack of sequence conservation therefore make functional interpretation of these newly discovered transcripts challenging. Many investigators have suggested the presence and importance of secondary structural elements within lncRNAs, but mammalian lncRNA secondary structure remains poorly understood. It is intriguing to speculate that in this group of genes, RNA secondary structures might be preserved throughout evolution and that this might explain the lack of sequence conservation among many lncRNAs. Scope of review Here, we review the extent of interspecies conservation among different lncRNAs, with a focus on a subset of lncRNAs that have been functionally investigated. The function of lncRNAs is widespread and we investigate whether different forms of functionalities may be conserved. Major conclusions Lack of conservation does not imbue a lack of function. We highlight several examples of lncRNAs where RNA structure appears to be the main functional unit and evolutionary constraint. We survey existing genomewide studies of mammalian lncRNA conservation and summarize their limitations. We further review specific human lncRNAs which lack evolutionary conservation beyond primates but have proven to be both functional and therapeutically relevant. General significance Pioneering studies highlight a role in lncRNAs for secondary structures, and possibly the presence of functional “modules”, which are interspersed with longer and less conserved stretches of nucleotide sequences. Taken together, high-throughput analysis of conservation and functional composition of the still-mysterious lncRNA genes is only now becoming feasible.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/a7c0a0decf3f7893eb9d3cebf4f9dbf2d04c36f3

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Citations in the corpus

DIANA-LncBase v2: indexing microRNA targets on non-coding transcripts (2015, background): “Users can add and remove search terms or filter [3] their results based on cell/tissue type and experimental”
Transcriptional and Post-transcriptional Gene Regulation by Long Non-coding RNA (2017, background): “However, some have argued that we should not apply the same criteria for sequence conservation to lncRNA as we do to coding genes because lack of sequence conservation does not in itself indicate lack of functional conservation [97] and evolution may act on lncRNA at another level [98].”