Role of circular RNAs in brain development and CNS diseases. (March 2020)

• Record Type: Journal Article
• Authors: Mehta, Suresh L.; Dempsey, Robert J.; Vemuganti, Raghu
• Is Part Of: Progress in neurobiology. Volume 186(2020)
• Publication Date: 2020-03
• Subjects: AD Alzheimer′s disease -- ADAR adenosine deaminase acting-on RNA -- ALS Amyotrophic lateral sclerosis -- APP amyloid precursor protein -- α-Syn α-synuclein -- Aβ amyloid-β -- BACE1 β‐site APP‐cleaving enzyme 1 -- BBB blood-brain barrier -- CDK2 cyclin-dependent kinase 2 -- CDR1 cerebellar degeneration‐related autoantigen 1 -- CDR1as CDR1, antisense -- circRNAs circular RNAs -- CNS central nervous system -- DBR1 debranching enzyme -- DCC Deleted in Colorectal Cancer -- ddPCR droplet digital PCR -- DHX9 DExD/H-box helicase 9 -- ETS-1 E26 transformation–specific sequence-1 -- FUS fused in sarcoma -- GO Gene Ontology -- GSK-3β glycogen synthase kinase-3β -- HI hypoxia-ischemia -- HIPK3 homeodomain interacting protein kinase 3 -- HNF1β hepatocyte nuclear factor-1β -- IRES internal ribosome entry site -- lncRNAs long noncoding RNAs -- m6A N6-methyladenosine -- MALAT1 Metastasis Associated Lung Adenocarcinoma Transcript 1 -- Mbl muscleblind -- MCAO middle cerebral artery occlusion -- MDD major depressive disorder -- METTL3 methyltransferase-like 3 -- miRNAs microRNAs -- MLL mixed-lineage leukemia -- MNs motor neurons -- MS Multiple sclerosis -- MSA Multiple system atrophy -- ncRNAs noncoding RNAs -- OGD oxygen glucose deprivation -- ORFs open reading frames -- PD Parkinson's disease -- PINT87aa 87 amino acid tumor-suppressive peptide -- PAF1 polymerase associated factor -- pre mRNA precursor mRNA -- Pol II polymerase II -- PRR11 proline-rich protein 11 -- RBPs RNA binding proteins -- RNA-FISH RNA fluorescence in situ hybridization -- ROS reactive oxygen species -- SCI spinal cord injury -- SIRT1 Sirtuin 1 -- SMN1 survival motor neuron 1 -- SOX13 SRY-Box 13 -- SRSF1 serine and arginine-rich splicing factor 1 -- SRY sex-determining region Y -- TBI traumatic brain injury -- TDP-43 TAR DNA binding protein 43 -- TGF-β transformed growth factor -- TIPARP 23, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly (ADP-ribose) polymerase -- TNF‐α tumor necrosis factor-α -- T-UCRs transcribed ultraconserved regions -- UBE2A Ubiquitin protein ligase A -- UCHL1 Ubiquitin C-Terminal Hydrolase L1 -- UTR untranslated region -- U1snRNP U1 small nuclear ribonucleoprotein particle -- VEGF-A Vascular endothelial growth factor A -- ZO-1 Zonula occludens-1; CircRNAs -- miRNAs -- Brain -- Development -- Cancer -- Acute and chronic neurodegeneration; Neurobiology -- Periodicals; Neurology -- Periodicals; Neurology -- Periodicals; Neurobiologie -- Périodiques; 612.8
• DOI: 10.1016/j.pneurobio.2020.101746
• Languages: English
• ISSNs: 0301-0082

Abstract

Graphical abstract: Highlights: Circular RNAs (circRNAs) are vastly conserved noncoding RNAs formed by back-splicing and covalent fusion of RNA free ends into natural circles. They are highly abundant, dynamically expressed, and spatiotemporally regulated in the healthy brain. Their brain expression steadily increases from embryonic to the adult stage. The putative functions of circRNAs are transcription regulation, miRNAs and ribonucleoproteins sequestration, and translation to peptides. Altered levels of circRNAs mediate brain diseases and degeneration. Abstract: In mammals, many classes of noncoding RNAs (ncRNAs) are expressed at a much higher level in the brain than in other organs. Recent studies have identified a new class of ncRNAs called circular RNAs (circRNAs), which are produced by back-splicing and fusion of either exons, introns, or both exon-intron into covalently closed loops. The circRNAs are also highly enriched in the brain and increase continuously from the embryonic to the adult stage. Although the functional significance and mechanism of action of circRNAs are still being actively explored, they are thought to regulate the transcription of their host genes and sequestration of miRNAs and RNA binding proteins. Some circRNAs are also shown to have translation potential to form peptides. The expression and abundance of circRNAs seem to be spatiotemporally maintained in a normal brain. Altered expression of circRNAs is also thought to mediate several disorders, including brain-tumor growth, and acute and chronic neurodegenerative disorders by affecting mechanisms such as angiogenesis, neuronal plasticity, autophagy, apoptosis, and inflammation. This review discusses the involvement of various circRNAs in brain development and CNS diseases. A better understanding of the circRNA function will help to develop novel therapeutic strategies to treat CNS complications.