Long noncoding RNAs (lncRNAs) have gained widespread attention in recent years as a potentially new and crucial layer of biological regulation. lncRNAs of all kinds have been implicated in a range of developmental processes and diseases, but knowledge of the mechanisms by which they act is still surprisingly limited, and claims that almost the entirety of the mammalian genome is transcribed into functional noncoding transcripts remain controversial. At the same time, a small number of well-studied lncRNAs have given us important clues about the biology of these molecules, and a few key functional and mechanistic themes have begun to emerge, although the robustness of these models and classification schemes remains to be seen. Here, we review the current state of knowledge of the lncRNA field, discussing what is known about the genomic contexts, biological functions, and mechanisms of action of lncRNAs. We also reflect on how the recent interest in lncRNAs is deeply rooted in biology's longstanding concern with the evolution and function of genomes.T HE past several years have witnessed a steep rise of interest in the study of lncRNAs. Almost on a weekly basis, it seems that a new lncRNA is found to be up-or downregulated in a particular disease, or a new class of noncoding transcripts is uncovered by a transcriptomic study, or a new article heralds a paradigm shift that lncRNAs will bring to our understanding of biology. Without a doubt, the advent of sensitive, high-throughput genomic technologies such as microarrays and next-generation sequencing (NGS) has resulted in an unprecedented ability to detect novel transcripts, the vast majority of which seem not to be derived from annotated protein-coding genes. Despite this explosion of data, however, surprisingly little is known about how lncRNAs function, how many different types of lncRNAs exist, or even whether most of them carry biological significance.In this review, we focus on recently discovered lncRNAs of .200 nt, place these new discoveries in historical context, and outline areas where additional work is needed. The review does not cover "classic" ncRNAs such as ribosomal (r) RNAs, ribozymes, transfer (t)RNAs, small nuclear (sn)RNAs, small nucleolar (sno)RNAs, and telomere-associated RNAs (TERC, TERRA); nor does it cover small ncRNAs such as microRNAs (miRNAs), endogenous small interfering (endo-si)RNAs that participate in RNA interference (RNAi), and Piwi-associated (pi)RNAs. We refer readers to the many

The inactive X chromosome (Xi) serves as a model to understand gene silencing on a global scale. Here, we perform “identification of direct RNA interacting proteins” (iDRiP) to isolate a comprehensive protein interactome for Xist, an RNA required for Xi silencing. We discover multiple classes of interactors, including cohesins, condensins, topoisomerases, RNA helicases, chromatin remodelers and modifiers, which synergistically repress Xi transcription. Inhibiting two or three interactors destabilizes silencing. While Xist attracts some interactors, it repels architectural factors. Xist evicts cohesins from the Xi and directs an Xi-specific chromosome conformation. Upon deleting Xist, the Xi acquires the cohesin-binding and chromosomal architecture of the active X. Our study unveils many layers of Xi repression and demonstrates a central role for RNA in the topological organization of mammalian chromosomes.