Secondary structure impacts patterns of selection in human lncRNAs

BMC Biology

Research Article

Cinta Pegueroles¹  Toni Gabaldón² 

[1] Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003, Barcelona, Spain;Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain;Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, 08003, Barcelona, Spain;Universitat Pompeu Fabra (UPF), 08003, Barcelona, Spain;Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluís Companys 23, 08010, Barcelona, Spain;

关键词: lncRNA;    Purifying selection;    Divergence;    Polymorphism;    Secondary structure;   

DOI  :  10.1186/s12915-016-0283-0

 received in 2016-05-24, accepted in 2016-07-04,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundMetazoans transcribe many long non-coding RNAs (lncRNAs) that are poorly conserved and whose function remains unknown. This has raised the questions of what fraction of the predicted lncRNAs is actually functional, and whether selection can effectively constrain lncRNAs in species with small effective population sizes such as human populations.ResultsHere we evaluate signatures of selection in human lncRNAs using inter-specific data and intra-specific comparisons from five major populations, as well as by assessing relationships between sequence variation and predictions of secondary structure. In all analyses we included a reference of functionally characterized lncRNAs. Altogether, our results show compelling evidence of recent purifying selection acting on both characterized and predicted lncRNAs. We found that RNA secondary structure constrains sequence variation in lncRNAs, so that polymorphisms are depleted in paired regions with low accessibility and tend to be neutral with respect to structural stability.ConclusionsImportant implications of our results are that secondary structure plays a role in the functionality of lncRNAs, and that the set of predicted lncRNAs contains a large fraction of functional ones that may play key roles that remain to be discovered.

【 授权许可】

CC BY   
© Pegueroles and Gabaldon. 2016