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.
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