Generic placeholder image

Current Alzheimer Research


ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Review Article

Research Progress on circRNA in Nervous System Diseases

Author(s): Nana Ma, Wei Zhang* and Jun Wan*

Volume 17 , Issue 8 , 2020

Page: [687 - 697] Pages: 11

DOI: 10.2174/1567205017666201111114928

Price: $65


Circular RNAs (circRNAs) are a kind of non-coding RNA molecule with highly stable circular structures. CircRNAs are primarily composed of exons and/or introns. Recently, a lot of exciting studies showed that circRNA played an essential role in the development of nervous system diseases. Here, classification, characteristics, biogenesis, and the association of circRNA dysregulation with nervous system diseases, such as Alzheimer’s disease, are summarized. The review not only contributes to a better understanding of circRNAs, but also provides new research directions toward the diagnosis, treatment, and prevention of nervous system diseases.

Keywords: Circular RNA, non-coding RNA, nervous system, disease, Alzheimer's disease, Parkinson disease.

An integrated encyclopedia of DNA elements in the human genome. Nature 2012; 489(7414): 57-74.
Zlotorynski E. The innate function of circular RNAs. Nat Rev Mol Cell Biol 2019; 7: 387.
Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet 2019; 11: 675-91.
Flemming A. The enigma of circular RNA. Nat Rev Immunol 2019; 6: 351.
Sun J, Li B, Shu C, Ma Q, Wang J. Functions and clinical significance of circular RNAs in glioma. Mol Cancer 2020; 1: 34.
Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 2013; 495(7441): 333-8.
Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 2013; 19(2): 141-57.
Bahn JH, Zhang Q, Li F, et al. The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva. Clin Chem 2015; 61(1): 221-30.
Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol 2014; 32(5): 453-61.
Salzman J, Chen RE, Olsen MN, Wang PL, Brown PO. Cell-type specific features of circular RNA expression. PLoS Genet 2013; 9(9)e1003777
Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PLoS One 2012; 7(2)e30733
Zheng Q, Bao C, Guo W, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun 2016; 7: 11215.
Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges. Nature 2013; 495(7441): 384-8.
Hansen TB, Wiklund ED, Bramsen JB, et al. miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. EMBO J 2011; 30(21): 4414-22.
Zhao ZJ, Shen J. Circular RNA participates in the carcinogenesis and the malignant behavior of cancer. RNA Biol 2017; 14(5): 514-21.
Ho-Xuan H, Glažar P, Latini C, et al. Comprehensive analysis of translation from overexpressed circular RNAs reveals pervasive translation from linear transcripts. Nucleic Acids Res 2020; 48(18): 10368-82.
Surono A, Takeshima Y, Wibawa T, Ikezawa M, Nonaka I, Matsuo M. Circular dystrophin RNAs consisting of exons that were skipped by alternative splicing. Hum Mol Genet 1999; 8(3): 493-500.
Abe N, Matsumoto K, Nishihara M, et al. Rolling circle translation of circular RNA in living human cells. Sci Rep 2015; 5: 16435.
Thompson SR. So you want to know if your message has an IRES? Wiley Interdiscip Rev RNA 2012; 3(5): 697-705.
Li Z, Huang C, Bao C, et al. Corrigendum: Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol 2017; 24(2): 194.
Ashwal-Fluss R, Meyer M, Pamudurti NR, et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell 2014; 56(1): 55-66.
Zhang Y, Zhang XO, Chen T, et al. Circular intronic long noncoding RNAs. Mol Cell 2013; 51(6): 792-806.
Yin QF, Yang L, Zhang Y, et al. Long noncoding RNAs with snoRNA ends. Mol Cell 2012; 48(2): 219-30.
Wang Y, Wang Z. Efficient backsplicing produces translatable circular mRNAs. RNA 2015; 21(2): 172-9.
Yang Y, Fan X, Mao M, et al. Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res 2017; 27(5): 626-41.
Rybak-Wolf A, Stottmeister C, Glažar P, et al. Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol Cell 2015; 58(5): 870-85.
You X, Vlatkovic I, Babic A, et al. Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci 2015; 18(4): 603-10.
Venø MT, Hansen TB, Venø ST, et al. Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development. Genome Biol 2015; 16: 245.
Szabo L, Morey R, Palpant NJ, Wang PL. Erratum to: Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development. Genome Biol 2016; 17(1): 263.
Gokool A, Anwar F, Voineagu I. The landscape of circular RNA expression in the human brain. Biol Psychiatry 2019. Biol Psychiatry 2020; 87(3): 294-304.
Dube U, Del-Aguila JL, Li Z, et al. Dominantly Inherited Alzheimer Network (DIAN). An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations. Nat Neurosci 2019; 22(11): 1903-12.
Maass PG, Gla Ar P, Memczak S, et al. A map of human circular RNAs in clinically relevant tissues. J Mol Med (Berl) 2017; 95(11): 1179-89.
Starling S. Alzheimer disease: Blood-derived Aβ induces AD pathology. Nat Rev Neurol 2018; 14(1): 2.
Lonskaya I, Shekoyan AR, Hebron ML, et al. Diminished parkin solubility and co-localization with intraneuronal amyloid-β are associated with autophagic defects in Alzheimer’s disease. J Alzheimers Dis 2013; 1: 231-47.
Bingol B, Sheng M. Deconstruction for reconstruction: The role of proteolysis in neural plasticity and disease. Neuron 2011; 69(1): 22-32.
Lukiw JW. Circular RNA (circRNA) in Alzheimer’s disease (AD). Front Genet 2013; 4: 307.
Tatro ET, Risbrough V, Soontornniyomkij B, et al. Short-term recognition memory correlates with regional CNS expression of microRNA-138 in mice. Am J Geriatr Psychiat Off J Am Assoc Geriatr Psychiat 2013; 5: 461-73.
Julia SD, Sara A, Marcel S, et al. MicroRNA-138 is a potential regulator of memory performance in humans. Front Hum Neurosci 2014; 8: 501.
Zimmerman AJ, Hafez AK, Amoah SK, et al. A psychiatric disease-related circular RNA controls synaptic gene expression and cognition. Mol Psychiatry 2020; 25(11): 2712-27.
Chokshi V, Gao M, Grier BD, et al. Input-specific metaplasticity in the visual cortex requires homer1a-mediated mGluR5 signaling. Neuron 2019; 104(4): 736-748.e6.
Zhang S, Zhu D, Li H, Li H, Feng C, Zhang W. Characterization of circRNA-associated-ceRNA networks in a senescence-accelerated mouse prone 8 brain. Mol Ther 2017; 25(9): 2053-61.
Ma N, Pan J, Ye X, Yu B, Zhang W, Wan J. Whole-transcriptome analysis of APP/PS1 mouse brain and identification of circRNA-miRNA-mRNA networks to investigate AD pathogenesis. Mol Ther Nucleic Acids 2019; 18: 1049-62.
Patrick S. Neuromodulatory procedures for gait disorders in Parkinson’s disease. Acta Neurol Belg 2018; 118(1): 13-9.
Junn E, Lee KW, Jeong BS, Chan TW, Im JY, Mouradian MM. Repression of alpha-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci USA 2009; 106(31): 13052-7.
Choi DC, Chae YJ, Kabaria S, et al. MicroRNA-7 protects against 1-methyl-4-phenylpyridinium-induced cell death by targeting RelA. J Neurosci 2014; 34(38): 12725-37.
Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP.
Danan M, Schwartz S, Edelheit S, Sorek R. Transcriptome-wide discovery of circular RNAs in Archaea. Nucleic Acids Res 2012; 40(7): 3131-42.
Cozzolino M, Ferri A, Valle C, Carrì MT. Mitochondria and ALS: Implications from novel genes and pathways. Mol Cell Neurosci 2013; 55: 44-9.
Pokrishevsky E, Grad LI, Yousefi M, Wang J, Mackenzie IR, Cashman NR. Aberrant localization of FUS and TDP43 is associated with misfolding of SOD1 in amyotrophic lateral sclerosis. PLoS One 2012; 7(4)e35050
Nishimoto Y, Nakagawa S, Hirose T, et al. The long non-coding RNA nuclear-enriched abundant transcript 1_2 induces paraspeckle formation in the motor neuron during the early phase of amyotrophic lateral sclerosis. Mol Brain 2013; 6: 31.
Roos RA. Huntington’s disease: A clinical review. Eur J Neurol 2018; 25(1): 24-34.
Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, et al. An RNA gene expressed during cortical development evolved rapidly in humans. Nature 2006; 443(7108): 167-72.
Xu K, Schadt EE, Pollard KS, Roussos P, Dudley JT. Genomic and network patterns of schizophrenia genetic variation in human evolutionary accelerated regions. Mol Biol Evol 2015; 5: 1148-60.
Hwang J-Y, Zukin RS. REST, a master transcriptional regulator in neurodegenerative disease. Curr Opin Neurobiol 2018; 48: 193-200.
Johnson R, Richter N, Jauch R, et al. Human accelerated region 1 noncoding RNA is repressed by REST in Huntington’s disease. Physiol Genomics 2010; 41(3): 269-74.
Lin N, Chang KY, Li Z, et al. An evolutionarily conserved long noncoding RNA TUNA controls pluripotency and neural lineage commitment. Mol Cell 2014; 53(6): 1005-19.
Francelle L, Galvan L, Gaillard MC. The striatal long non-coding RNA Abhd11os is neuroprotective against an N-terminal fragment of mutant huntingtin in-vivo. Neurobiol Aging 2015; 3: 1601-7.
Li Y, Zheng Q, Bao C, et al. Circular RNA is enriched and stable in exosomes: A promising biomarker for cancer diagnosis. Cell Res 2015; 25(8): 981-4.
Qin M, Liu G, Huo X, et al. Hsa_circ_0001649: A circular RNA and potential novel biomarker for hepatocellular carcinoma. Cancer Biomark 2016; 16(1): 161-9.
Dropcho EJ, Chen YT, Posner JB, Old LJ. Cloning of a brain protein identified by autoantibodies from a patient with paraneoplastic cerebellar degeneration. Proc Natl Acad Sci USA 1987; 84(13): 4552-6.
Hansen TB, Kjems J, Damgaard CK. Circular RNA and miR-7 in cancer. Cancer Res 2013; 73(18): 5609-12.
Liu Z, Jiang Z, Huang J, et al. miR-7 inhibits glioblastoma growth by simultaneously interfering with the PI3K/ATK and Raf/MEK/ERK pathways. Int J Oncol 2014; 44(5): 1571-80.
Burd CE, Jeck WR, Liu Y, et al. Expression of linear and novel circular forms of an INK4/ARF-associated non-coding RNA correlates with atherosclerosis risk. PLoS Genet 2010; 6(12)e1001233
Wu F, Han B, Wu S, et al. Circular RNA TLK1 aggravates neuronal injury and neurological deficits after ischemic stroke via miR-335-3p/TIPARP. J Neurosci 2019; 39(37): 7369-93.
Wang M, Yu F, Wu W, et al. Circular RNAs: A novel type of non-coding RNA and their potential implications in antiviral immunity. Int J Biol Sci 2017; 13(12): 1497-506.
Chen YG, Kim MV, Chen X, et al. Sensing self and foreign circular RNAs by intron identity. Mol Cell 2017; 67(2): 228-238.e5.
He L, Zhang A, Xiong L, et al. Deep circular RNA sequencing provides insights into the mechanism underlying grass carp reovirus infection. Int J Mol Sci 2017; 18(9): 9.
Wang YH, Yu XH, Luo SS, Han H. Comprehensive circular RNA profiling reveals that circular RNA100783 is involved in chronic CD28-associated CD8(+)T cell ageing. Immun Ageing 2015; 12: 17.
Fu D, Yu W, Li M, et al. MicroRNA-138 regulates the balance of Th1/Th2 via targeting RUNX3 in psoriasis. Immunol Lett 2015; 166(1): 55-62.
Prusiner SB. The prion diseases. Brain Pathol 1998; 8(3): 499-513.
Satoh J, Yamamura T. Gene expression profile following stable expression of the cellular prion protein. Cell Mol Neurobiol 2004; 24(6): 793-814.
Satoh J, Obayashi S, Misawa T, Sumiyoshi K, Oosumi K, Tabunoki H. Protein microarray analysis identifies human cellular prion protein interactors. Neuropathol Appl Neurobiol 2009; 35(1): 16-35.
Cui X, Niu W, Kong L, et al. hsa_circRNA_103636: potential novel diagnostic and therapeutic biomarker in Major depressive disorder. Biomarkers Med 2016; 10(9): 943-52.
Khodor YL, Menet JS, Tolan M, Rosbash M. Cotranscriptional splicing efficiency differs dramatically between Drosophila and mouse. RNA 2012; 12: 2174-86.
Cheng L, Zhao W, Hill AF. Exosomes and their role in the intercellular trafficking of normal and disease associated prion proteins. Mol Aspects Med 2018; 60: 62-8.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy