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Fig. 1 | Biological Research

Fig. 1

From: Noncoding RNAs in skeletal development and disorders

Fig. 1

Biogenesis and functions of circRNAs, miRNAs, and lncRNAs. The precursors of most circRNAs, miRNAs, and lncRNAs are transcribed by polymerase II (Pol II) in a manner similar to that of linear mRNAs. During transcription, most human genes undergo competition between linear splicing and backsplicing of exons. Backsplicing is often favored due to factors, such as long flanking introns, inverted repeat elements (such as Alu), and RBPs [53]. The close proximity of a downstream splice-donor site (SD) with an upstream splice-acceptor site (SA) is achieved through the base pairing of inverted repeat elements or the dimerization of RBPs, leading to backsplicing. This process involves an upstream branch point (BP) attacking a downstream SD site, which in turn attacks an upstream SA site, ultimately resulting in the formation of exon-intron circRNAs or exonic circRNAs. CircRNAs have been shown to modulate cellular signaling transduction by interacting with signaling proteins, inhibiting miRNA functions, and serving as a template for the production of functional proteins. Within the nucleus, primary miRNA transcripts (pri-mRNAs) undergo cleavage mediated by the microprocessor complex Drosha–DGCR8, generating precursor miRNAs (pre-miRNAs) [16]. These pre-miRNAs are subsequently transported to the cytoplasm by exportin 5 [19, 20]. Once in the cytoplasm, pre-miRNAs undergo further cleavage by the enzyme Dicer, resulting in the formation of miRNA duplexes. These duplexes then associate with AGO proteins, thereby assembling the RNA-induced silencing complex (RISC). Once loaded onto RISC, miRNAs may undergo further processing, ultimately leading to their engagement with target messenger RNA (mRNA). Such interactions may result in mRNA destabilization or translational repression, representing key steps in post-transcriptional gene regulation. LncRNAs are transcribed and processed like mRNAs. However, many lncRNAs are retained in the nucleus to regulate the mRNA metabolism or form subnuclear domains. In the cytoplasm, lncRNA also modulates cellular signaling transduction by interacting with signaling proteins, inhibiting miRNA functions, and serving as a template for the production of functional peptides [6]

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