Decoding lncRNA functions using high-throughput pathway perturbation.

Abstract
Genome-wide studies have shown that our genome is pervasively transcribed, producing a complex pool of coding and non-coding transcripts that shape a cell’s transcriptome. Long non-coding RNAs or lncRNAs dominate the non-coding transcriptome and are emerging as key regulatory factors in human disease and development. Still, only a fraction of lncRNAs has been studied experimentally. In order to gain insights in lncRNA functions on a genome-wide scale, we performed high-throughput pathway perturbations followed by total RNA sequencing. Cells were treated with 90 targeted compounds and 90 transcription factor siRNAs, yielding a total of 180 individual perturbations. For each perturbation, differentially expressed lncRNAs were identified and mapped to pathways using matching protein-coding gene expression data. We define a functional context for thousands of lncRNAs that can serve as a starting point to guide more focused experimental studies and accelerate lncRNA research.