Fig. 1.

Biogenesis and function of miRNAs, lncRNAs and circRNAs. a MIRNAs are transcribed as primary miRNAs (pri-miRNAs) that contain the characteristic stem-loop structure. Pri-miRNAs are processed in the nucleus by Drosha and DGCR8 and transformed into precursor miRNAs (pre-miRNAs). Pre-miRNAs are transported from the nucleus to the cytoplasm via Exportin 5 and then are turned into an miRNA duplex after being cleaved by Dicer. One strand of the miRNA duplex is incorporated as part of the miRNA-induced silencing complex (RISC), and the second strand is degraded. By base-pairings between miRNAs and their target mRNA, the RISC binds an mRNA and suppresses its translation or induces its degradation. Additionally, there are unconventional/atypical miRNA functions such as activating Toll-like receptors (TLRs), binding non-AGO proteins, binding other ncRNAs (sponging), and regulating transcription. b Most lncRNAs have a biogenesis similar to mRNAs (although several exceptions exist), being capped, spliced, and adenylated. The mature lncRNAs adopt complex 3D structures that give them their multivalent functions. The function of lncRNAs can be divided according to their cellular localization: bound to chromatin (often cis functions), intranuclear (usually trans functions), and intracytoplasmic (trans functions). LncRNAs bound to chromatin usually function as regulators of transcription and induce chromosome looping and histone modifications. Nuclear lncRNAs can assemble paraspeckles and interact with nuclear proteins. Cytoplasmic lncRNAs bind mRNAs and act as decoys, guides, and scaffolds to transcriptionally or post-transcriptionally regulate downstream target genes, bind proteins to modify their function and stability, code for micropeptides that are being translated, and bind other ncRNA species (including miRNAs). c CircRNAs have multiple biogenesis mechanisms, but a common event for all is back-splicing. Back-splicing can be induced by protein dimerization, sequence complementarity of flanking introns, exon skipping mechanisms, and intron lariat debranching. After forming an uninterrupted RNA loop, the transcript is exported into the cytoplasm, where it serves as an miRNA sponge that inhibits miRNAs to regulate the expression of target genes, as a decoy of RNA-binding proteins to modulate gene expression or translation, or as a platform for protein-protein interaction; additionally, these transcripts also can be translated into micropeptides. As observed, there is direct crosstalk between lncRNAs and miRNAs and between circRNAs and miRNAs via sponging, creating a network of ncRNA molecules.