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Circular RNAs in Brain Physiology and Disease

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Circular RNAs

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1087))

Abstract

Circular RNAs (circRNAs) are endogenously expressed non-coding RNAs discovered in the early 1990s as a transcriptional by-product of little importance. It was only recently that they were identified as a key player in regulating the gene expression by targeting and modulating the functions of microRNA, a process known as microRNA sponging. They are distributed throughout the system in a tissue-specific manner showing abundant enrichment in neuronal tissue. Their physiological functions in the brain such as neuronal maturation, differentiation, etc. as well as their implications in numerous brain-related disorders have made its entry into the spotlight. Yet the wider scope and molecular mechanism of circRNAs still remain elusive. In this chapter, we describe in detail the functional aspects and importance of circRNAs in the human brain and how it is associated with various neurological diseases.

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Abbreviations

circRNAs:

Circular RNAs

GBM:

Glioblastoma multiforme

MDD:

Major depressive disorder

microRNAs:

MicroRNAs

mRNA:

Messenger RNA

MSA:

Multiple system atrophy

ncRNA:

Non-coding RNA

pre-mRNA:

Precursor mRNA

SRSF1:

Serine- and arginine-rich splicing factor 1

TBI:

Traumatic brain injury

References

  1. Wang PL, Bao Y, Yee MC et al (2014) Circular RNA is expressed across the eukaryotic tree of life. PLoS One 9(6):e90859

    Article  PubMed  PubMed Central  Google Scholar 

  2. Chen LL (2016) The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol 17(4):205–211

    Article  CAS  PubMed  Google Scholar 

  3. Greene J, Baird AM, Brady L et al (2017) Circular RNAs: biogenesis, function and role in human diseases. Front Mol Biosci 4:38

    Article  PubMed  PubMed Central  Google Scholar 

  4. Salzman J, Chen RE, Olsen MN et al (2013) Cell-type specific features of circular RNA expression. PLoS Genet 9(9):e1003777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rybak-Wolf A, Stottmeister C, Glazar P et al (2015) Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol Cell 58(5):870–885

    Article  CAS  PubMed  Google Scholar 

  6. 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):1966–1980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. 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):603–610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hanan M, Soreq H, Kadener S (2017) CircRNAs in the brain. RNA Biol 14(8):1028–1034

    Article  PubMed  Google Scholar 

  9. Chen W, Schuman E (2016) Circular RNAs in brain and other tissues: a functional enigma. Trends Neurosci 39(9):597–604

    Article  CAS  PubMed  Google Scholar 

  10. Chen BJ, Yang B, Janitz M (2018) Region-specific expression of circular RNAs in the mouse brain. Neurosci Lett 666:44–47

    Article  CAS  PubMed  Google Scholar 

  11. Reddy AS, O'Brien D, Pisat N et al (2017) A comprehensive analysis of cell type-specific nuclear RNA from neurons and glia of the brain. Biol Psychiatry 81(3):252–264

    Article  CAS  PubMed  Google Scholar 

  12. Gruner H, Cortes-Lopez M, Cooper DA et al (2016) CircRNA accumulation in the aging mouse brain. Sci Rep 6:38907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Daniel C, Silberberg G, Behm M et al (2014) Alu elements shape the primate transcriptome by cis-regulation of RNA editing. Genome Biol 15(2):R28

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hansen TB, Jensen TI, Clausen BH et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495(7441):384–388

    Article  CAS  PubMed  Google Scholar 

  15. van Rossum D, Verheijen BM, Pasterkamp RJ (2016) Circular RNAs: novel regulators of neuronal development. Front Mol Neurosci 9:74

    PubMed  PubMed Central  Google Scholar 

  16. Liu C, Zhang C, Yang J et al (2017) Screening circular RNA expression patterns following focal cerebral ischemia in mice. Oncotarget 8(49):86535–86547

    PubMed  PubMed Central  Google Scholar 

  17. 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):52–56

    Article  CAS  PubMed  Google Scholar 

  18. Mehta SL, Pandi G, Vemuganti R (2017) Circular RNA Expression Profiles Alter Significantly in Mouse Brain After Transient Focal Ischemia. Stroke 48(9):2541–2548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bai Y, Zhang Y, Han B et al (2018) Circular RNA DLGAP4 ameliorates ischemic stroke outcomes by targeting miR-143 to regulate endothelial-mesenchymal transition associated with blood-brain barrier integrity. J Neurosci 38(1):32–50

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Zheng J, Liu X, Xue Y et al (2017) TTBK2 circular RNA promotes glioma malignancy by regulating miR-217/HNF1beta/Derlin-1 pathway. J Hematol Oncol 10(1):52

    Article  PubMed  PubMed Central  Google Scholar 

  21. Yang P, Qiu Z, Jiang Y et al (2016) Silencing of cZNF292 circular RNA suppresses human glioma tube formation via the Wnt/beta-catenin signaling pathway. Oncotarget 7(39):63449–63455

    PubMed  PubMed Central  Google Scholar 

  22. Yang Y, Gao X, Zhang M et al (2018) Novel role of FBXW7 circular RNA in repressing glioma tumorigenesis. J Natl Cancer Inst 110(3)

    Google Scholar 

  23. Zhu J, Ye J, Zhang L et al (2017) Differential expression of circular RNAs in glioblastoma multiforme and its correlation with prognosis. Transl Oncol 10(2):271–279

    Article  PubMed  PubMed Central  Google Scholar 

  24. Barbagallo D, Caponnetto A, Cirnigliaro M et al (2018) CircSMARCA5 inhibits migration of glioblastoma multiforme cells by regulating a molecular axis involving splicing factors SRSF1/SRSF3/PTB. Int J Mol Sci 19(2)

    Article  PubMed Central  Google Scholar 

  25. Shi Z, Chen T, Yao Q et al (2017) The circular RNA ciRS-7 promotes APP and BACE1 degradation in an NF-kappaB-dependent manner. FEBS J 284(7):1096–1109

    Article  CAS  PubMed  Google Scholar 

  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):116

    Article  Google Scholar 

  27. Kumar L, Shamsuzzama, Jadiya P et al (2018) Functional characterization of novel circular RNA molecule, circzip-2 and its synthesizing gene zip-2 in C. elegans model of Parkinson’s disease. Mol Neurobiol. https://doi.org/10.1007/s12035-018-0903-5

    Article  CAS  PubMed  Google Scholar 

  28. Chen BJ, Mills JD, Takenaka K et al (2016) Characterization of circular RNAs landscape in multiple system atrophy brain. J Neurochem 139(3):485–496

    Article  CAS  PubMed  Google Scholar 

  29. Cui X, Niu W, Kong L et al (2016) hsa_circRNA_103636: potential novel diagnostic and therapeutic biomarker in Major depressive disorder. Biomark Med 10(9):943–952

    Article  CAS  PubMed  Google Scholar 

  30. Cardamone G, Paraboschi EM, Rimoldi V et al (2017) The characterization of GSDMB splicing and backsplicing profiles identifies novel isoforms and a circular RNA that are dysregulated in multiple sclerosis. Int J Mol Sci 18(3)

    Article  PubMed Central  Google Scholar 

  31. Iparraguirre L, Munoz-Culla M, Prada-Luengo I et al (2017) Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis. Hum Mol Genet 26(18):3564–3572

    Article  CAS  PubMed  Google Scholar 

  32. Huang R, Zhang Y, Han B et al (2017) Circular RNA HIPK2 regulates astrocyte activation via cooperation of autophagy and ER stress by targeting MIR124-2HG. Autophagy 13(10):1722–1741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Competing Financial Interests

The authors declare no competing financial interests.

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Authors and Affiliations

  1. School of Biotechnology, National Institute of Technology Calicut, Calicut, India

    S. Gokul & G. K. Rajanikant

Authors
  1. S. Gokul
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  2. G. K. Rajanikant
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Correspondence to G. K. Rajanikant .

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Editors and Affiliations

  1. School of Life Science, Institute of Cardiovascular Sciences, Shanghai University, Shanghai, China

    Junjie Xiao

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Gokul, S., Rajanikant, G.K. (2018). Circular RNAs in Brain Physiology and Disease. In: Xiao, J. (eds) Circular RNAs. Advances in Experimental Medicine and Biology, vol 1087. Springer, Singapore. https://doi.org/10.1007/978-981-13-1426-1_18

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