Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans
Autor: | Aleksandra E. Kornienko, Christoph P. Dotter, Philipp M. Guenzl, Florian M. Pauler, Heinz Gisslinger, Robert Kralovics, Denise P. Barlow, Bettina Gisslinger, Ciara Cleary |
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Jazyk: | angličtina |
Předmět: |
0301 basic medicine
lncRNAs Gene Expression expression variation Biology Genome Transcriptome Open Reading Frames 03 medical and health sciences Genetic variation Gene expression Humans natural variation RNA Messenger Gene lncRNA features Genetics 576 Genetics and evolution Genome Human Research Genetic Variation Molecular Sequence Annotation lncRNA identification granulocytes Human genetics human genome annotation 030104 developmental biology RNA splicing RNA Long Noncoding Human genome |
Zdroj: | Genome Biology |
ISSN: | 1474-760X |
DOI: | 10.1186/s13059-016-0873-8 |
Popis: | Background Long non-coding RNAs (lncRNAs) are increasingly implicated as gene regulators and may ultimately be more numerous than protein-coding genes in the human genome. Despite large numbers of reported lncRNAs, reference annotations are likely incomplete due to their lower and tighter tissue-specific expression compared to mRNAs. An unexplored factor potentially confounding lncRNA identification is inter-individual expression variability. Here, we characterize lncRNA natural expression variability in human primary granulocytes. Results We annotate granulocyte lncRNAs and mRNAs in RNA-seq data from 10 healthy individuals, identifying multiple lncRNAs absent from reference annotations, and use this to investigate three known features (higher tissue-specificity, lower expression, and reduced splicing efficiency) of lncRNAs relative to mRNAs. Expression variability was examined in seven individuals sampled three times at 1- or more than 1-month intervals. We show that lncRNAs display significantly more inter-individual expression variability compared to mRNAs. We confirm this finding in two independent human datasets by analyzing multiple tissues from the GTEx project and lymphoblastoid cell lines from the GEUVADIS project. Using the latter dataset we also show that including more human donors into the transcriptome annotation pipeline allows identification of an increasing number of lncRNAs, but minimally affects mRNA gene number. Conclusions A comprehensive annotation of lncRNAs is known to require an approach that is sensitive to low and tight tissue-specific expression. Here we show that increased inter-individual expression variability is an additional general lncRNA feature to consider when creating a comprehensive annotation of human lncRNAs or proposing their use as prognostic or disease markers. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-0873-8) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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