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

Area of Science:

• Genomics and Transcriptomics
• Molecular Biology
• Bioinformatics

Background:

• Long non-coding RNAs (lncRNAs) are critical gene regulators, potentially outnumbering protein-coding genes.
• Current lncRNA annotations may be incomplete due to their low, tissue-specific expression patterns.
• Inter-individual expression variability is an understudied factor in lncRNA identification.

Purpose of the Study:

• To characterize natural expression variability of lncRNAs in human primary granulocytes.
• To investigate lncRNA features, including tissue-specificity, expression levels, and splicing efficiency, relative to mRNAs.
• To assess the impact of inter-individual variability on lncRNA annotation.

Main Methods:

• RNA sequencing (RNA-seq) of primary granulocytes from 10 healthy individuals.
• Analysis of lncRNA and mRNA expression, tissue-specificity, expression levels, and splicing efficiency.
• Examination of expression variability across 7 individuals sampled multiple times.
• Validation using independent datasets from GTEx (multiple tissues) and GEUVADIS (lymphoblastoid cell lines).

Main Results:

• Identified novel lncRNAs not present in existing reference annotations.
• Demonstrated significantly higher inter-individual expression variability in lncRNAs compared to mRNAs.
• Confirmed increased lncRNA variability across multiple tissues and cell lines.
• Showed that increasing donor numbers enhances lncRNA identification but minimally impacts mRNA annotation.

Conclusions:

• Comprehensive lncRNA annotation requires sensitivity to low, tissue-specific expression and inter-individual variability.
• Inter-individual expression variability is a general feature of lncRNAs.
• Understanding lncRNA variability is crucial for accurate annotation and development of prognostic/disease markers.