circRNA Array Service
circRNA array is a method for profiling and analyzing circular RNAs in organisms. Circular RNA (circRNA) is a unique type of RNA that, in contrast to linear RNA, forms a covalently closed continuous loop, some of which are relatively abundant in the eukaryotic transcriptome. The majority of these circRNAs are derived from exonic or intronic sequences, are conserved between species, and frequently exhibit tissue/developmental stage-specific expression. Due to their greater nuclease stability, circular RNAs are more stable than linear RNAs, which represents a tremendous therapeutic advantage as a unique class of biomarkers. In addition, it has been demonstrated that circRNAs operate as natural miRNA sponge transcripts, also known as competitive endogenous RNAs (ceRNAs), in numerous species. Their interaction with illness-related miRNAs highlights the potential role of circular RNAs in disease regulation.
Fig.1 Biogenesis of circular RNAs. (Santer, 2019)
Functions of circRNA
Some circRNAs may have important non-coding functions that are related to how stable they are. This is because the third position of codons, which is usually not very stable because the genetic code is redundant, is more stable in some circRNAs than in exons that are not part of circRNAs. But only a small number of those that are thought to work as miRNA sponges have had their biological functions researched. Crosslinking immunoprecipitation data sets also show that circRNAs interact with many RNA-binding proteins to act as protein sponges, improve protein function, act as scaffolds to help enzymes and substrates form complexes, and bring proteins to specific sites. Also, even though most circRNAs are thought to be non-coding, a small number of them can translate without a cap in some situations.
Fig.2 General mechanisms of circRNA functions. (Kristensen, 2019)
Published Data
| Paper Title | Targeting mitochondria-located circRNA SCAR alleviates NASH via reducing mROS output |
| Journal | Cell |
| Published | 2020 |
| Abstract | Immunometabolic diseases involve mitochondria's genome. Without a delivery system, mitochondria-located noncoding RNAs' functions are unknown. They found that mitochondrial circRNAs make up a significant portion of downregulated circRNAs in liver fibroblasts of nonalcoholic steatohepatitis (NASH) patients. Using mitochondria-targeting nanoparticles, they found that Steatohepatitis-associated circRNA ATP5B Regulator (SCAR) in mitochondria inhibits mitochondrial ROS (mROS) output and fibroblast activation. PGC-1a-mediated circRNA SCAR binds to ATP5B and blocks CypD-mPTP interaction, shutting down mPTP. ER stress-induced CHOP inhibits PGC-1a in lipid overload. Targeting circRNA SCAR reduces high-fat diet-induced cirrhosis and insulin resistance in vivo. circRNA SCAR promotes steatosis-to-NASH progression. They identify a mitochondrial circRNA that drives metaflammation and targets NASH treatment. |
| Result |
They compared the profiles of circRNA expression in primary fibroblasts from four patients with NASH cirrhosis and four patients without NAFLD. In NASH fibroblasts, 15 circRNAs were consistently upregulated and 11 were consistently downregulated. Four out of eleven downregulated circRNAs were surprisingly encoded by the mitochondrial genome, despite nuclear circRNAs comprising the vast majority of the entire circRNomics. The suppression of three mitochondrial circRNAs (mito-circRNAs) in NASH patients was validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in a separate cohort of 18 patients with NASH cirrhosis and 20 patients without NAFLD. These 3 mito-circRNAs are generated from the mitochondrial genome via a "back-splicing" mechanism, as shown by the fractionation experiment. Despite hsa_circ_0089763 retaining an intron between exons, all mature transcripts contain exonic sequences. hsa_circ_0089762 and hsa_circ_0089763 are produced from the light strand of mito-DNA, whereas hsa_circ_0008882 is produced from the heavy strand.
|
Fig.3 Lipid exposure induces mitochondrial circRNomics imbalance in fibroblasts. (Zhao, 2020)
Creative Biolabs provides a platform for profiling, analyzing, and exploring this new and interesting world of non-coding RNAs by systematically evaluating the expression of circRNAs. From sample to publishable data, we provide specialist circRNA array services. For more information, please contact us.
Fig.4 Experiment workflow of the microarray expression profile of circular RNAs. (Qu, 2015)
References
- Santer, L.; et al. Circular RNAs: a novel class of functional RNA molecules with a therapeutic perspective. Molecular Therapy. 2019, 27(8): 1350-1363.
- Kirstensen, L.S.; et al. The biogenesis, biology and characterization of circular RNAs. Nature Reviews Genetics. 2019, 20: 675-691.
- Qu, S.B.; et al. Microarray expression profile of circular RNAs in human pancreatic ductal adenocarcinoma. Genomics Data. 2015, 5: 385-387.
- Zhao, Q.Y.; et al. Targeting mitochondrial-located circRNA SCAR alleviates NASH via reducing mROS output. Cell. 2020, 183:1-18.
