Although backsplicing of pre-messenger RNA (pre-mRNA) exons is inefficiently processed by the classical spliceosomal machinery, this backsplicing generates circular RNAs (circRNAs) genome-wide. These RNAs are nearly identical in sequence to linear RNAs originating from the same gene locus, differing only at the backsplicing junction (BSJ) site.
Importantly, increasing evidence indicates that some circRNAs play important roles in gene expression regulation through diverse molecular modes of action. These include regulating transcription, interfering with mRNA splicing, acting as "sponges" to absorb miRNAs or proteins, influencing translation, and being translated into peptides. Several highly expressed circRNAs have been implicated in maintaining quiescent hematopoietic stem cells, regulating cell growth and cancer progression, influencing brain function and neuronal development, and modulating innate immune responses. These findings add to the complexity and diversity of the human transcriptome.
| Cat.No. | Product Name | Price |
|---|---|---|
| PMCR-0001 | EGFP circRNA | Inquiry |
| PMCR-0002 | Firefly Luciferase circRNA | Inquiry |
| PMCR-0003 | Gaussia Luciferase circRNA | Inquiry |
| PMCR-0004 | Renilla Luciferase circRNA | Inquiry |
| PMCR-0005 | mCherry circRNA | Inquiry |
| PMCR-0006 | β-galactosidase circRNA | Inquiry |
| PMCR-0007 | Luciferase P2A GFP circRNA | Inquiry |
| PMCR-0008 | Cas9 circRNA | Inquiry |
| PMCR-0009 | NLS-Cre circRNA | Inquiry |
| PMCR-0010 | Cas9 Nickase circRNA | Inquiry |
| PMCR-0011 | Cas9-T2A-EGFP circRNA | Inquiry |
| PMCR-0012 | Cre-T2A-EGFP circRNA | Inquiry |
| PMCR-0013 | OVA circRNA | Inquiry |
| PMCR-0014 | EPO circRNA | Inquiry |
| PMCR-0019 | p53 circRNA | Inquiry |
| PMCR-0020 | PD1 circRNA | Inquiry |
Furthermore, alternative circularization (AC) results in the generation of multiple circRNAs from a single gene locus. This further expands the functional complexity of circRNAs and contributes to distinct circRNA expression profiles in different cell lines and tissues. However, the functions of most circRNAs generated through alternative circularization remain unknown.
Recently, researchers published a research paper titled "Direct circMAN1A2(2,3,4,5)-CENPB mRNA interaction regulates cell proliferation and cancer progression" in the journal Nature Communications. The study identified circMAN1A2(2,3,4,5), a circRNA generated through alternative circularization, that is highly expressed in tumors. The study revealed that circMAN1A2(2,3,4,5) regulates colorectal cancer development through RNA-RNA interactions, and blocking this interaction could inhibit colorectal cancer progression.
In this new study, a research team systematically profiled the alternative circularization (AC) landscape across multiple cell lines and colorectal cancer (CRC) tissues, identifying the predominantly expressed circular RNAs (pe-circRNAs) within each AC locus. The results revealed that while most of the top-ranked pe-circRNAs exhibited cell type-specific expression, circMAN1A2 (2, 3, 4, 5), which was ubiquitously expressed across all samples, plays a crucial role in cell proliferation and CRC progression.
Figure 1. Repression of circMAN1A2(2,3,4,5) inhibits colorectal cancer cell proliferation and tumor progression. (Cao M, et al., 2025)
Mechanistically, circMAN1A2(2,3,4,5) directly interacts with the 3' untranslated region (3' UTR) of CENPB mRNA through its unique reverse splicing junction site, thereby enhancing IGF2BP2-mediated CENPB mRNA stability. The research team further demonstrated that using locked nucleic acids (LNAs) to target the reverse splicing site of circMAN1A2(2,3,4,5) inhibited the direct interaction between circMAN1A2(2,3,4,5) and CENPB mRNA, thereby suppressing colorectal cancer progression.
Overall, this study reveals the prevalence of alternative circularization (AC) and the regulatory role of a specific alternatively circularized circRNA, circMAN1A2(2,3,4,5), in cell proliferation and tumor progression.
Reference
Cao M, et al. Direct circMAN1A2 (2, 3, 4, 5)-CENPB mRNA interaction regulates cell proliferation and cancer progression. Nature Communications, 2025, 16(1): 8609.