Long non-coding RNAs in the nucleolus: Biogenesis, regulation, and function.

The nucleolus functions as a multi-layered regulatory hub for ribosomal RNA (rRNA) biogenesis and ribosome assembly. Long noncoding RNAs (lncRNAs) in the nucleolus, originated from transcription by different RNA polymerases, have emerged as critical players in not only fine-tuning rRNA transcription and processing, but also shaping the organization of the multi-phase nucleolar condensate. Here, we review the diverse molecular mechanisms by which functional lncRNAs operate in the nucleolus, as well as their profound implications in a variety of biological processes. We also highlight the development of emerging molecular tools for characterizing and manipulating RNA function in living cells, and how application of such tools in the nucleolus might enable the discovery of additional insights and potential therapeutic strategies.