The nucleolus is the largest sub-nuclear domain, serving primarily as the place for ribosome biogenesis. A delicately regulated function of the nucleolus is vital to the cell not only for maintaining proper protein synthesis but is also tightly associated with responses to different types of cellular stresses. Recently, several long non-coding RNAs (lncRNAs) were found to be part of the regulatory network that modulate nucleolar functions. Several of these lncRNAs are encoded in the ribosomal DNA (rDNA) repeats or are transcribed from the genomic regions that are located near the nucleolus organizer regions (NORs). In this review, we first discuss the current understanding of the sequence of the NORs and variations between different NORs. We then focus on the NOR-derived lncRNAs in mammalian cells and their functions in rRNA transcription and the organization of nucleolar structure under different cellular conditions. The identification of these lncRNAs reveals great potential of the NORs in harboring novel genes involved in the regulation of nucleolar functions.
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