Mammalian genomes encode tens of thousands of long noncoding RNAs (lncRNAs) that have been implicated in a diverse array of biological processes and human diseases. In recent years, the development of new tools for studying lncRNAs has enabled important progress in defining the mechanisms by which Xist and other lncRNAs function. This collective work provides a framework for how to define the mechanisms by which lncRNAs act. This includes defining lncRNA function, identifying and characterizing lncRNA-protein interactions, and lncRNA localization in the cell. In this review, we discuss various experimental approaches for deciphering lncRNA mechanisms and discuss issues and limitations in interpreting these results. We explore what these data can reveal about lncRNA function and mechanism as well as emerging insights into lncRNA biology that have been derived from these studies.
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