Abstract
Long noncoding RNAs (lncRNAs) can positively and negatively regulate expression of target genes encoded in cis. However, the extent, characteristics and mechanisms of such cis- regulatory lncRNAs (cis-lncRNAs) remain obscure. Until now, they have been defined using inconsistent, ad hoc criteria that can result in false-positive predictions. Here, we introduce TransCistor, a framework for defining and identifying cis-lncRNAs based on enrichment of targets amongst proximal genes. Using transcriptome-wide perturbation experiments for 190 human and 133 mouse lncRNAs, we provide the first large-scale view of cis-lncRNAs. Our results ascribe cis- regulatory activity to only a small fraction (~10%) of lncRNAs, with a prevalence of activators over repressors. Cis-lncRNAs are detected at similar rates by RNA interference (RNAi) and antisense oligonucleotide (ASO) perturbations. We leverage this cis-lncRNA catalogue to evaluate mechanistic models for cis-lncRNAs involving enhancers and chromatin folding. Thus, TransCistor places cis-regulatory lncRNAs on a quantitative foundation for the first time.
Competing Interest Statement
The authors have declared no competing interest.
