Circular RNAs pp 205-213 | Cite as

Circular RNAs and Neuronal Development

  • Lena ConstantinEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1087)


Circular RNAs (circRNAs) are abundant in the brain and are often expressed in complex spatiotemporal patterns that coincide with distinct developmental transitions. This suggests that circRNAs play a significant role in the central nervous system. This book chapter will review research progress into the function of circRNAs during neuronal development. The major themes to be discussed are the enrichment of circRNAs in the synapse and their possible contributions to synaptopathologies, in addition to the findings that neural circRNAs accumulate with age and appear beneficial for neuronal repair. Although more research is needed, some of the possible functions of circRNAs with in the brain are already beginning to come to light.


Circular RNA Brain Synapse Ageing Alzheimer’s disease Ischemic stroke 



I would like to thank Professor Brandon J. Wainwright for encouraging me to pursue noncoding RNAs as a field of research.

Competing Financial Interests

The author declares no competing financial interests.


  1. 1.
    You X, Vlatkovic I, Babic A et al (2015) Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci 18(4):603–610CrossRefGoogle Scholar
  2. 2.
    Rybak-Wolf A, Stottmeister C, Glazar P et al (2015) Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. gs. Mol Cell 58(5):870–885CrossRefGoogle Scholar
  3. 3.
    Veno MT, Hansen TB, Veno ST et al (2015) Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development. Genome Biol 16:245CrossRefGoogle Scholar
  4. 4.
    Westholm JO, Miura P, Olson S et al (2014) Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation. Cell Rep 9(5):1966–1980CrossRefGoogle Scholar
  5. 5.
    Xia S, Feng J, Lei L et al (2017) Comprehensive characterization of tissue-specific circular RNAs in the human and mouse genomes. Brief Bioinform 18(6):984–992Google Scholar
  6. 6.
    Li L, Zheng YC, Kayani MUR et al (2017) Comprehensive analysis of circRNA expression profiles in humans by RAISE. Int J Oncol 51(6):1625–1638CrossRefGoogle Scholar
  7. 7.
    King IF, Yandava CN, Mabb AM et al (2013) Topoisomerases facilitate transcription of long genes linked to autism. Nature 501(7465):58–62CrossRefGoogle Scholar
  8. 8.
    Mabb AM, Kullmann PH, Twomey MA et al (2014) Topoisomerase 1 inhibition reversibly impairs synaptic function. Proc Natl Acad Sci U S A 111(48):17290–17295CrossRefGoogle Scholar
  9. 9.
    Zhang XO, Wang HB, Zhang Y et al (2014) Complementary sequence-mediated exon circularization. Cell 159(1):134–147CrossRefGoogle Scholar
  10. 10.
    Jeck WR, Sorrentino JA, Wang K et al (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 19(2):141–157CrossRefGoogle Scholar
  11. 11.
    Gruner H, Cortes-Lopez M, Cooper DA et al (2016) CircRNA accumulation in the aging mouse brain. Sci Rep 6:38907CrossRefGoogle Scholar
  12. 12.
    Bachmayr-Heyda A, Reiner AT, Auer K et al (2015) Correlation of circular RNA abundance with proliferation—exemplified with colorectal and ovarian cancer, idiopathic lung fibrosis, and normal human tissues. Sci Rep 5:8057CrossRefGoogle Scholar
  13. 13.
    Hu JH, Park JM, Park S et al (2010) Homeostatic scaling requires group I mGluR activation mediated by Homer1a. Neuron 68(6):1128–1142CrossRefGoogle Scholar
  14. 14.
    Tu JC, Xiao B, Yuan JP et al (1998) Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Neuron 21 (4):717–726; Brakeman PR, Lanahan AA, O’Brien R et al (1997) Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 386 (6622):284–288CrossRefGoogle Scholar
  15. 15.
    Ashwal-Fluss R, Meyer M, Pamudurti NR et al (2014) circRNA biogenesis competes with pre-mRNA splicing. Mol Cell 56(1):55–66PubMedPubMedCentralGoogle Scholar
  16. 16.
    Selkoe DJ (2002) Alzheimer’s disease is a synaptic failure. Science 298(5594):789–791CrossRefGoogle Scholar
  17. 17.
    Davies CA, Mann DM, Sumpter PQ et al (1987) A quantitative morphometric analysis of the neuronal and synaptic content of the frontal and temporal cortex in patients with Alzheimer’s disease. J Neurol Sci 78(2):151–164CrossRefGoogle Scholar
  18. 18.
    Terry RD, Masliah E, Salmon DP et al (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30(4):572–580CrossRefGoogle Scholar
  19. 19.
    Zhang S, Zhu D, Li H et al (2017) Characterization of circRNA-associated-ceRNA networks in a senescence-accelerated mouse prone 8 brain. Mol Ther 25(9):2053–2061CrossRefGoogle Scholar
  20. 20.
    Calza L, Fernandez M, Giuliani A et al (2002) Thyroid hormone activates oligodendrocyte precursors and increases a myelin-forming protein and NGF content in the spinal cord during experimental allergic encephalomyelitis. Proc Natl Acad Sci U S A 99(5):3258–3263CrossRefGoogle Scholar
  21. 21.
    Humphries CE, Kohli MA, Nathanson L et al (2015) Integrated whole transcriptome and DNA methylation analysis identifies gene networks specific to late-onset Alzheimer’s disease. J Alzheimers Dis 44(3):977–987CrossRefGoogle Scholar
  22. 22.
    Yamanaka Y, Faghihi MA, Magistri M et al (2015) Antisense RNA controls LRP1 sense transcript expression through interaction with a chromatin-associated protein, HMGB2. Cell Rep 11(6):967–976CrossRefGoogle Scholar
  23. 23.
    Guo JU, Agarwal V, Guo H et al (2014) Expanded identification and characterization of mammalian circular RNAs. Genome Biol 15(7):409CrossRefGoogle Scholar
  24. 24.
    Memczak S, Jens M, Elefsinioti A et al (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495(7441):333–338CrossRefGoogle Scholar
  25. 25.
    Lukiw WJ (2013) Circular RNA (circRNA) in Alzheimer’s disease (AD). Front Genet 4:307PubMedPubMedCentralGoogle Scholar
  26. 26.
    Zhao Y, Alexandrov PN, Jaber V et al (2016) Deficiency in the ubiquitin conjugating enzyme UBE2A in Alzheimer’s disease (AD) is linked to deficits in a natural circular miRNA-7 sponge (circRNA; ciRS-7). Genes (Basel) 7(12):116CrossRefGoogle Scholar
  27. 27.
    Hansen TB, Jensen TI, Clausen BH et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495 (7441):384–388; Junn E, Lee KW, Jeong BS et al (2009) Repression of alpha-synuclein expression and toxicity by microRNA-7. Proc Natl Acad Sci U S A 106 (31):13052–13057CrossRefGoogle Scholar
  28. 28.
    Guo J (2014) Transcription: the epicenter of gene expression. J Zhejiang Univ Sci B 15(5):409–411CrossRefGoogle Scholar
  29. 29.
    Drinnenberg IA, Fink GR, Bartel DP (2011) Compatibility with killer explains the rise of RNAi-deficient fungi. Science 333(6049):1592CrossRefGoogle Scholar
  30. 30.
    Wang PL, Bao Y, Yee MC et al (2014) Circular RNA is expressed across the eukaryotic tree of life. PLoS One 9(6):e90859CrossRefGoogle Scholar
  31. 31.
    Mazin P, Xiong J, Liu X et al (2013) Widespread splicing changes in human brain development and aging. Mol Syst Biol 9:633; Harries LW, Hernandez D, Henley W et al (2011) Human aging is characterized by focused changes in gene expression and deregulation of alternative splicing. Aging Cell 10 (5):868–878Google Scholar
  32. 32.
    Mehta SL, Pandi G, Vemuganti R (2017) Circular RNA expression profiles alter significantly in mouse brain after transient focal ischemia. Stroke 48(9):2541–2548CrossRefGoogle Scholar
  33. 33.
    Liu C, Zhang C, Yang J et al (2017) Screening circular RNA expression patterns following focal cerebral ischemia in mice. Oncotarget 8(49):86535–86547PubMedPubMedCentralGoogle Scholar
  34. 34.
    Lin SP, Ye S, Long Y et al (2016) Circular RNA expression alterations are involved in OGD/R-induced neuron injury. Biochem Biophys Res Commun 471(1):52–56CrossRefGoogle Scholar
  35. 35.
    Xie B, Wang Y, Lin Y et al (2018) Circular RNA expression profiles alter significantly after traumatic brain injury in rats. J Neurotrauma. CrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Faculty of Medicine, School of Biomedical SciencesThe University of QueenslandSt LuciaAustralia

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