Global Positioning System: Understanding Long Noncoding RNAs through Subcellular Localization

The localization of long noncoding RNAs (lncRNAs) within the cell is the primary determinant of their molecular functions. LncRNAs are often thought of as chromatin-restricted regulators of gene transcription and chromatin structure. However, a rich population of cytoplasmic lncRNAs has come to light, with diverse roles including translational regulation, signaling, and respiration. RNA maps of increasing resolution and scope are revealing a subcellular world of highly specific localization patterns and hint at sequence-based address codes specifying lncRNA fates. We propose a new framework for analyzing sequencing-based data, which suggests that numbers of cytoplasmic lncRNA molecules rival those in the nucleus. New techniques promise to create high-resolution, transcriptome-wide maps associated with all organelles of the mammalian cell. Given its intimate link to molecular roles, subcellular localization provides a means of unlocking the mystery of lncRNA functions.