Figure 1.

An overview of lncRNA biogenesis. At the chromatin level, lncRNA promoters have higher levels of H3K4me3, H3K27ac, and H3K9ac, which are more strongly repressed by chromatin remodeling complexes such as Swr1, Isw2, Rsc, and Ino80. The transcription of lncRNA starts when the SWI/SNF chromatin remodeling complex facilitate access of RNA polymerase II (Pol II) to the core promoter, while the elongation stage is controlled by MYC and DICER1, and its synthesis is complete by 3′-polyadenylation. Then, synthesized lncRNAs should be spliced, capped, and/or polyadenylated by recruiting proteins. This procedure is mediated by regions within the immature lncRNAs such as polyadenylation signal regions. Many Pol II-transcribed lncRNAs are not efficiently processed and are retained in the nucleus. Binding to the nuclear retention element is another mechanism leading to the retention of lncRNAs in the nucleus. Nuclear organization, regulation of gene transcription, alternative splicing, and chromatin remodulation are the main functions of lncRNAs in the nucleus. Other lncRNAs are spliced and exported to the cytoplasm by nuclear RNA export factor 1 (NXF1). In the cytoplasm, lncRNAs typically interact with a variety of RBPs. Some of them are sorted into mitochondria, some of them are associated with ribosomes, and others reside in organelles, such as exosomes. As one of the main mechanisms of action of lncRNA-mediated mRNA stability regulation, lncRNAs can directly bind to their target mRNAs and avoid interactions with ribosomes.