Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans

Kornienko, Aleksandra E and Dotter, Christoph P and Guenzl, Philipp M and Gisslinger, Heinz and Gisslinger, Bettina and Cleary, Ciara and Kralovics, Robert and Pauler, Florian M and Barlow, Denise P (2016) Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biology, 17 (1). Article number: 14 . ISSN 1474-7596

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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.

Item Type: Article
DOI: 10.1186/s13059-016-0873-8
Uncontrolled Keywords: transcriptome, Expression variation, Granulocytes, Human genome annotation, lncRNA features, lncRNA identification, lncRNAs, Natural variation
Subjects: 500 Science > 570 Life sciences; biology > 576 Genetics and evolution
SWORD Depositor: Sword Import User
Depositing User: Sword Import User
Date Deposited: 06 Dec 2016 13:25
Last Modified: 05 Sep 2017 09:13
URI: https://repository.ist.ac.at/id/eprint/709

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