In search for multifunctional lncRNAs

Abstract

Long non-coding RNAs (lncRNAs) were so named because at the time of their discovery, no corresponding protein products were known. Despite the lack of evidence for translation, many lncRNAs perform essential cellular functions such as regulation of gene expression. Recent studies show that many lncRNAs, including those with known regulatory functions, bind to ribosomes and are translated, suggesting that RNAs can perform two different kinds of functions (a phenomenon known in proteins, called moonlighting). Using a formal mathematical model, I show that execution of one function limits that of the other. However, an RNA can transition from one function to the other, simply by a spatiotemporal regulation of its interacting partners. I further studied the properties of proteins encoded in functional human lncRNAs and found that many of them have complex sequences, and some of them can even adopt stable 3D structures. These findings may encourage further exploration of moonlighting lncRNAs, their regulation, and their role in the evolution of new protein coding genes.