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DOI: 10.1055/s-0039-1692680
Long Noncoding RNAs of the Arterial Wall as Therapeutic Agents and Targets in Atherosclerosis
Funding This work was in part funded by the German Research Foundation (DFG) as part of the Collaborative Research Center CRC1123 “Atherosclerosis - Mechanisms and Networks of Novel Therapeutic Targets” (project B1) and by the Leducq-foundation CADgenomics.Publication History
15 November 2018
23 April 2019
Publication Date:
16 July 2019 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201908/lookinside/thumbnails/10-1055-s-0039-1692680_180810-1.jpg)
Abstract
Long noncoding ribonucleic acids (lncRNAs) have been defined as transcripts which are > 200 ribonucleotides in size and are not translated into protein. Recent work has shown that many lncRNAs do have specific molecular functions and biological effects, and are involved in a growing number of diseases, including atherosclerosis. As a consequence, lncRNAs are also becoming interesting targets for therapeutic intervention. Here, we focus on lncRNAs which are expressed in the arterial wall, and describe potential RNA therapeutic approaches of atherosclerosis by manipulating lncRNAs without affecting genome deoxyribonucleic acid content: Starting out with an overview of all lncRNAs that have so far been implicated in atherosclerosis by in vivo studies, we describe methodologies for their activation, inactivation, and RNA sequence manipulation. We continue by addressing how artificial (nonnative) therapeutic lncRNAs may be designed, and which molecular functions these designer lncRNAs may exploit. We conclude with an outlook on approaches for chemical lncRNA modification, RNA mass production, and site-specific therapeutic delivery.
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References
- 1 Bertone P, Stolc V, Royce TE. , et al. Global identification of human transcribed sequences with genome tiling arrays. Science 2004; 306 (5705): 2242-2246
- 2 Carninci P, Kasukawa T, Katayama S. , et al; FANTOM Consortium; RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group). The transcriptional landscape of the mammalian genome. Science 2005; 309 (5740): 1559-1563
- 3 Birney E, Stamatoyannopoulos JA, Dutta A. , et al; ENCODE Project Consortium; NISC Comparative Sequencing Program; Baylor College of Medicine Human Genome Sequencing Center; Washington University Genome Sequencing Center; Broad Institute; Children's Hospital Oakland Research Institute. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 2007; 447 (7146): 799-816
- 4 Djebali S, Davis CA, Merkel A. , et al. Landscape of transcription in human cells. Nature 2012; 489 (7414): 101-108
- 5 Hon CC, Ramilowski JA, Harshbarger J. , et al. An atlas of human long non-coding RNAs with accurate 5′ ends. Nature 2017; 543 (7644): 199-204
- 6 Maurano MT, Humbert R, Rynes E. , et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 2012; 337 (6099): 1190-1195
- 7 Andersson R, Gebhard C, Miguel-Escalada I. , et al. An atlas of active enhancers across human cell types and tissues. Nature 2014; 507 (7493): 455-461
- 8 Ørom UA, Derrien T, Beringer M. , et al. Long noncoding RNAs with enhancer-like function in human cells. Cell 2010; 143 (01) 46-58
- 9 Barrett SP, Salzman J. Circular RNAs: analysis, expression and potential functions. Development 2016; 143 (11) 1838-1847
- 10 Holdt LM, Kohlmaier A, Teupser D. Molecular roles and function of circular RNAs in eukaryotic cells. Cell Mol Life Sci 2018; 75 (06) 1071-1098
- 11 Engreitz JM, Haines JE, Perez EM. , et al. Local regulation of gene expression by lncRNA promoters, transcription and splicing. Nature 2016; 539 (7629): 452-455
- 12 Lai F, Orom UA, Cesaroni M. , et al. Activating RNAs associate with Mediator to enhance chromatin architecture and transcription. Nature 2013; 494 (7438): 497-501
- 13 Huber F, Bunina D, Gupta I. , et al. Protein abundance control by non-coding antisense transcription. Cell Reports 2016; 15 (12) 2625-2636
- 14 Yang L, Lin C, Liu W. , et al. ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell 2011; 147 (04) 773-788
- 15 Yamazaki T, Souquere S, Chujo T. , et al. Functional domains of NEAT1 architectural lncRNA induce paraspeckle assembly through phase separation. Mol Cell 2018; 70 (06) 1038-1053
- 16 Denzler R, McGeary SE, Title AC, Agarwal V, Bartel DP, Stoffel M. Impact of microRNA levels, target-site complementarity, and cooperativity on competing endogenous RNA-regulated gene expression. Mol Cell 2016; 64 (03) 565-579
- 17 Chu C, Zhang QC, da Rocha ST. , et al. Systematic discovery of Xist RNA binding proteins. Cell 2015; 161 (02) 404-416
- 18 Holdt LM, Stahringer A, Sass K. , et al. Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Commun 2016; 7: 12429
- 19 Yap KL, Li S, Muñoz-Cabello AM. , et al. Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a. Mol Cell 2010; 38 (05) 662-674
- 20 Holdt LM, Hoffmann S, Sass K. , et al. Alu elements in ANRIL non-coding RNA at chromosome 9p21 modulate atherogenic cell functions through trans-regulation of gene networks. PLoS Genet 2013; 9 (07) e1003588
- 21 Zhou X, Han X, Wittfeldt A. , et al. Long non-coding RNA ANRIL regulates inflammatory responses as a novel component of NF-κB pathway. RNA Biol 2016; 13 (01) 98-108
- 22 Chen R, Kong P, Zhang F. , et al. EZH2-mediated α-actin methylation needs lncRNA TUG1, and promotes the cortex cytoskeleton formation in VSMCs. Gene 2017; 616: 52-57
- 23 Su IH, Dobenecker MW, Dickinson E. , et al. Polycomb group protein ezh2 controls actin polymerization and cell signaling. Cell 2005; 121 (03) 425-436
- 24 Sharma S, Findlay GM, Bandukwala HS. , et al. Dephosphorylation of the nuclear factor of activated T cells (NFAT) transcription factor is regulated by an RNA-protein scaffold complex. Proc Natl Acad Sci U S A 2011; 108 (28) 11381-11386
- 25 Li J, Chen C, Ma X. , et al. Long noncoding RNA NRON contributes to HIV-1 latency by specifically inducing tat protein degradation. Nat Commun 2016; 7: 11730
- 26 Wesselhoeft RA, Kowalski PS, Anderson DG. Engineering circular RNA for potent and stable translation in eukaryotic cells. Nat Commun 2018; 9 (01) 2629
- 27 Sampath K, Ephrussi A. CncRNAs: RNAs with both coding and non-coding roles in development. Development 2016; 143 (08) 1234-1241
- 28 Lanz RB, McKenna NJ, Onate SA. , et al. A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex. Cell 1999; 97 (01) 17-27
- 29 Candeias MM, Malbert-Colas L, Powell DJ. , et al. P53 mRNA controls p53 activity by managing Mdm2 functions. Nat Cell Biol 2008; 10 (09) 1098-1105
- 30 Cheng Z, Otto GM, Powers EN. , et al. Pervasive, coordinated protein-level changes driven by transcript isoform switching during meiosis. Cell 2018; 172 (05) 910-923
- 31 Van Dalfsen KM, Hodapp S, Keskin A. , et al. Global proteome remodeling during ER stress involves Hac1-driven expression of long undecoded transcript isoforms. Dev Cell 2018; 46 (02) 219-235
- 32 Chia M, Tresenrider A, Chen J. , et al. Transcription of a 5′ extended mRNA isoform directs dynamic chromatin changes and interference of a downstream promoter. eLife 2017; 6: 6
- 33 Shan K, Liu C, Liu BH. , et al. Circular noncoding RNA HIPK3 mediates retinal vascular dysfunction in diabetes mellitus. Circulation 2017; 136 (17) 1629-1642
- 34 Liu C, Yao MD, Li CP. , et al. Silencing of circular RNA-ZNF609 ameliorates vascular endothelial dysfunction. Theranostics 2017; 7 (11) 2863-2877
- 35 Chen L, Yang W, Guo Y. , et al. Exosomal lncRNA GAS5 regulates the apoptosis of macrophages and vascular endothelial cells in atherosclerosis. PLoS One 2017; 12 (09) e0185406
- 36 Tang R, Zhang G, Wang YC, Mei X, Chen SY. The long non-coding RNA GAS5 regulates transforming growth factor β (TGF-β)-induced smooth muscle cell differentiation via RNA Smad-binding elements. J Biol Chem 2017; 292 (34) 14270-14278
- 37 Han Y, Ma J, Wang J, Wang L. Silencing of H19 inhibits the adipogenesis and inflammation response in ox-LDL-treated Raw264.7 cells by up-regulating miR-130b. Mol Immunol 2018; 93: 107-114
- 38 Li DY, Busch A, Jin H. , et al. H19 induces abdominal aortic aneurysm development and progression. Circulation 2018; 138 (15) 1551-1568
- 39 Hofmann P, Sommer J, Theodorou K. , et al. Long non-coding RNA H19 regulates endothelial cell aging via inhibition of Stat3 signaling. Cardiovasc Res 2019; 115 (01) 230-242
- 40 Vigetti D, Deleonibus S, Moretto P. , et al. Natural antisense transcript for hyaluronan synthase 2 (HAS2-AS1) induces transcription of HAS2 via protein O-GlcNAcylation. J Biol Chem 2014; 289 (42) 28816-28826
- 41 van den Boom M, Sarbia M, von Wnuck Lipinski K. , et al. Differential regulation of hyaluronic acid synthase isoforms in human saphenous vein smooth muscle cells: possible implications for vein graft stenosis. Circ Res 2006; 98 (01) 36-44
- 42 Peng Y, Meng K, Jiang L. , et al. Thymic stromal lymphopoietin-induced HOTAIR activation promotes endothelial cell proliferation and migration in atherosclerosis. Biosci Rep 2017; 37 (04) BSR20170351
- 43 Liu J, Huang GQ, Ke ZP. Silence of long intergenic noncoding RNA HOTAIR ameliorates oxidative stress and inflammation response in ox-LDL-treated human macrophages by upregulating miR-330-5p. J Cell Physiol 2019; 234 (04) 5134-5142
- 44 Liao B, Chen R, Lin F. , et al. Long noncoding RNA HOTTIP promotes endothelial cell proliferation and migration via activation of the Wnt/β-catenin pathway. J Cell Biochem 2018; 119 (03) 2797-2805
- 45 Huang C, Hu YW, Zhao JJ. , et al. Long noncoding RNA HOXC-AS1 suppresses ox-LDL-induced cholesterol accumulation through promoting HOXC6 expression in THP-1 macrophages. DNA Cell Biol 2016; 35 (11) 722-729
- 46 Miao Y, Ajami NE, Huang TS. , et al. Enhancer-associated long non-coding RNA LEENE regulates endothelial nitric oxide synthase and endothelial function. Nat Commun 2018; 9 (01) 292
- 47 Rapicavoli NA, Qu K, Zhang J, Mikhail M, Laberge RM, Chang HY. A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics. eLife 2013; 2: e00762
- 48 Zhang DD, Wang WT, Xiong J. , et al. Long noncoding RNA LINC00305 promotes inflammation by activating the AHRR-NF-κB pathway in human monocytes. Sci Rep 2017; 7: 46204
- 49 Zhang BY, Jin Z, Zhao Z. Long intergenic noncoding RNA 00305 sponges miR-136 to regulate the hypoxia induced apoptosis of vascular endothelial cells. Biomed Pharmacother 2017; 94: 238-243
- 50 Carpenter S, Aiello D, Atianand MK. , et al. A long noncoding RNA mediates both activation and repression of immune response genes. Science 2013; 341 (6147): 789-792
- 51 Hu G, Gong AY, Wang Y. , et al. LincRNA-Cox2 promotes late inflammatory gene transcription in macrophages through modulating SWI/SNF-mediated chromatin remodeling. J Immunol 2016; 196 (06) 2799-2808
- 52 Covarrubias S, Robinson EK, Shapleigh B. , et al. CRISPR/Cas-based screening of long non-coding RNAs (lncRNAs) in macrophages with an NF-κB reporter. J Biol Chem 2017; 292 (51) 20911-20920
- 53 Hu YW, Yang JY, Ma X. , et al. A lincRNA-DYNLRB2-2/GPR119/GLP-1R/ABCA1-dependent signal transduction pathway is essential for the regulation of cholesterol homeostasis. J Lipid Res 2014; 55 (04) 681-697
- 54 Wu G, Cai J, Han Y. , et al. LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing p53 activity. Circulation 2014; 130 (17) 1452-1465
- 55 Arslan S, Berkan Ö, Lalem T. , et al; Cardiolinc™ networ. Long non-coding RNAs in the atherosclerotic plaque. Atherosclerosis 2017; 266: 176-181
- 56 Gast M, Rauch BH, Nakagawa S. , et al. Immune system-mediated atherosclerosis caused by deficiency of long noncoding RNA MALAT1 in ApoE−/− mice. Cardiovasc Res 2019; 115 (02) 302-314
- 57 Lino Cardenas CL, Kessinger CW, Cheng Y. , et al. An HDAC9-MALAT1-BRG1 complex mediates smooth muscle dysfunction in thoracic aortic aneurysm. Nat Commun 2018; 9 (01) 1009
- 58 Leisegang MS, Fork C, Josipovic I. , et al. Long noncoding RNA MANTIS facilitates endothelial angiogenic function. Circulation 2017; 136 (01) 65-79
- 59 Wu Z, He Y, Li D. , et al. Long noncoding RNA MEG3 suppressed endothelial cell proliferation and migration through regulating miR-21. Am J Transl Res 2017; 9 (07) 3326-3335
- 60 Zhou Y, Zhong Y, Wang Y. , et al. Activation of p53 by MEG3 non-coding RNA. J Biol Chem 2007; 282 (34) 24731-24742
- 61 Sallam T, Jones M, Thomas BJ. , et al. Transcriptional regulation of macrophage cholesterol efflux and atherogenesis by a long noncoding RNA. Nat Med 2018; 24 (03) 304-312
- 62 Yan B, Yao J, Liu JY. , et al. lncRNA-MIAT regulates microvascular dysfunction by functioning as a competing endogenous RNA. Circ Res 2015; 116 (07) 1143-1156
- 63 Zhao J, Zhang W, Lin M. , et al. MYOSLID is a novel serum response factor-dependent long noncoding RNA that amplifies the vascular smooth muscle differentiation program. Arterioscler Thromb Vasc Biol 2016; 36 (10) 2088-2099
- 64 Ahmed ASI, Dong K, Liu J. , et al. Long noncoding RNA NEAT1 (nuclear paraspeckle assembly transcript 1) is critical for phenotypic switching of vascular smooth muscle cells. Proc Natl Acad Sci U S A 2018; 115 (37) E8660-E8667
- 65 Sun J, Chen G, Jing Y. , et al. LncRNA expression profile of human thoracic aortic dissection by high-throughput sequencing. Cell Physiol Biochem 2018; 46 (03) 1027-1041
- 66 Krawczyk M, Emerson BM. p50-associated COX-2 extragenic RNA (PACER) activates COX-2 gene expression by occluding repressive NF-κB complexes. eLife 2014; 3: e01776
- 67 Shan K, Jiang Q, Wang XQ. , et al. Role of long non-coding RNA-RNCR3 in atherosclerosis-related vascular dysfunction. Cell Death Dis 2016; 7 (06) e2248
- 68 Shahmoradi N, Nasiri M, Kamfiroozi H, Kheiry MA. Association of the rs555172 polymorphism in SENCR long non-coding RNA and atherosclerotic coronary artery disease. J Cardiovasc Thorac Res 2017; 9 (03) 170-174
- 69 Boulberdaa M, Scott E, Ballantyne M. , et al. A role for the long noncoding RNA SENCR in commitment and function of endothelial cells. Mol Ther 2016; 24 (05) 978-990
- 70 Ballantyne MD, Pinel K, Dakin R. , et al. Smooth muscle enriched long noncoding RNA (SMILR) regulates cell proliferation. Circulation 2016; 133 (21) 2050-2065
- 71 Man HSJ, Sukumar AN, Lam GC. , et al. Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA. Proc Natl Acad Sci U S A 2018; 115 (10) 2401-2406
- 72 Li Z, Chao TC, Chang KY. , et al. The long noncoding RNA THRIL regulates TNFα expression through its interaction with hnRNPL. Proc Natl Acad Sci U S A 2014; 111 (03) 1002-1007
- 73 Zhang L, Cheng H, Yue Y, Li S, Zhang D, He R. TUG1 knockdown ameliorates atherosclerosis via up-regulating the expression of miR-133a target gene FGF1. Cardiovasc Pathol 2018; 33: 6-15
- 74 Chen C, Cheng G, Yang X, Li C, Shi R, Zhao N. Tanshinol suppresses endothelial cells apoptosis in mice with atherosclerosis via lncRNA TUG1 up-regulating the expression of miR-26a. Am J Transl Res 2016; 8 (07) 2981-2991
- 75 Yin D, Fu C, Sun D. Silence of lncRNA UCA1 represses the growth and tube formation of human microvascular endothelial cells through miR-195. Cell Physiol Biochem 2018; 49 (04) 1499-1511
- 76 Guo J, Cai H, Zheng J. , et al. Long non-coding RNA NEAT1 regulates permeability of the blood-tumor barrier via miR-181d-5p-mediated expression changes in ZO-1, occludin, and claudin-5. Biochim Biophys Acta Mol Basis Dis 2017; 1863 (09) 2240-2254
- 77 Ackers-Johnson M, Talasila A, Sage AP. , et al. Myocardin regulates vascular smooth muscle cell inflammatory activation and disease. Arterioscler Thromb Vasc Biol 2015; 35 (04) 817-828
- 78 Chen DD, Hui LL, Zhang XC, Chang Q. NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in macrophages through inhibiting miR-128. J Cell Biochem 2018; DOI: 10.1002/jcb.27541.
- 79 Bennett MR, Sinha S, Owens GK. Vascular smooth muscle cells in atherosclerosis. Circ Res 2016; 118 (04) 692-702
- 80 Yu CK, Xu T, Assoian RK, Rader DJ. Mining the stiffness-sensitive transcriptome in human vascular smooth muscle cells identifies long noncoding RNA stiffness regulators. Arterioscler Thromb Vasc Biol 2018; 38 (01) 164-173
- 81 Gast M, Schroen B, Voigt A. , et al. Long noncoding RNA MALAT1-derived mascRNA is involved in cardiovascular innate immunity. J Mol Cell Biol 2016; 8 (02) 178-181
- 82 Zhang X, Tang X, Liu K, Hamblin MH, Yin KJ. Long noncoding RNA Malat1 regulates cerebrovascular pathologies in ischemic stroke. J Neurosci 2017; 37 (07) 1797-1806
- 83 Xin JW, Jiang YG. Long noncoding RNA MALAT1 inhibits apoptosis induced by oxygen-glucose deprivation and reoxygenation in human brain microvascular endothelial cells. Exp Ther Med 2017; 13 (04) 1225-1234
- 84 Arun G, Diermeier S, Akerman M. , et al. Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev 2016; 30 (01) 34-51
- 85 Michalik KM, You X, Manavski Y. , et al. Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth. Circ Res 2014; 114 (09) 1389-1397
- 86 Hauser AT, Robaa D, Jung M. Epigenetic small molecule modulators of histone and DNA methylation. Curr Opin Chem Biol 2018; 45: 73-85
- 87 Gilbert LA, Larson MH, Morsut L. , et al. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 2013; 154 (02) 442-451
- 88 Qi LS, Larson MH, Gilbert LA. , et al. Repurposing CRISPR as an RNA-guided platform for sequence-specific control of gene expression. Cell 2013; 152 (05) 1173-1183
- 89 Ashwal-Fluss R, Meyer M, Pamudurti NR. , et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell 2014; 56 (01) 55-66
- 90 Zhang Y, Xue W, Li X. , et al. The biogenesis of nascent circular RNAs. Cell Reports 2016; 15 (03) 611-624
- 91 Zhang XO, Wang HB, Zhang Y, Lu X, Chen LL, Yang L. Complementary sequence-mediated exon circularization. Cell 2014; 159 (01) 134-147
- 92 Burd CE, Jeck WR, Liu Y, Sanoff HK, Wang Z, Sharpless NE. 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
- 93 Almontashiri NA, Antoine D, Zhou X. , et al. 9p21.3 coronary artery disease risk variants disrupt TEAD transcription factor-dependent transforming growth factor β regulation of p16 expression in human aortic smooth muscle cells. Circulation 2015; 132 (21) 1969-1978
- 94 Miller CL, Pjanic M, Wang T. , et al. Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci. Nat Commun 2016; 7: 12092
- 95 Mumbach MR, Satpathy AT, Boyle EA. , et al. Enhancer connectome in primary human cells identifies target genes of disease-associated DNA elements. Nat Genet 2017; 49 (11) 1602-1612
- 96 Scotti MM, Swanson MS. RNA mis-splicing in disease. Nat Rev Genet 2016; 17 (01) 19-32
- 97 Goettsch C, Rauner M, Hamann C. , et al. Nuclear factor of activated T cells mediates oxidised LDL-induced calcification of vascular smooth muscle cells. Diabetologia 2011; 54 (10) 2690-2701
- 98 von Lukowicz T, Hassa PO, Lohmann C. , et al. PARP1 is required for adhesion molecule expression in atherogenesis. Cardiovasc Res 2008; 78 (01) 158-166
- 99 Chen YG, Satpathy AT, Chang HY. Gene regulation in the immune system by long noncoding RNAs. Nat Immunol 2017; 18 (09) 962-972
- 100 Tabas I, Lichtman AH. Monocyte-macrophages and T cells in atherosclerosis. Immunity 2017; 47 (04) 621-634
- 101 Jost I, Shalamova LA, Gerresheim GK, Niepmann M, Bindereif A, Rossbach O. Functional sequestration of microRNA-122 from Hepatitis C Virus by circular RNA sponges. RNA Biol 2018; 15 (08) 1032-1039
- 102 Spitale RC, Flynn RA, Zhang QC. , et al. Structural imprints in vivo decode RNA regulatory mechanisms. Nature 2015; 519 (7544): 486-490
- 103 Randrianjatovo-Gbalou I, Rosario S, Sismeiro O. , et al. Enzymatic synthesis of random sequences of RNA and RNA analogues by DNA polymerase theta mutants for the generation of aptamer libraries. Nucleic Acids Res 2018; 46 (12) 6271-6284
- 104 Pastor F, Kolonias D, Giangrande PH, Gilboa E. Induction of tumour immunity by targeted inhibition of nonsense-mediated mRNA decay. Nature 2010; 465 (7295): 227-230
- 105 Nelson BR, Makarewich CA, Anderson DM. , et al. A peptide encoded by a transcript annotated as long noncoding RNA enhances SERCA activity in muscle. Science 2016; 351 (6270): 271-275
- 106 Gajewski TF, Schreiber H, Fu YX. Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol 2013; 14 (10) 1014-1022
- 107 Bäck M, Hansson GK. Anti-inflammatory therapies for atherosclerosis. Nat Rev Cardiol 2015; 12 (04) 199-211
- 108 Chen YG, Kim MV, Chen X. , et al. Sensing self and foreign circular RNAs by Intron identity. Mol Cell 2017; 67 (02) 228-238
- 109 Coffman RL, Sher A, Seder RA. Vaccine adjuvants: putting innate immunity to work. Immunity 2010; 33 (04) 492-503
- 110 Wang L, Smith D, Bot S, Dellamary L, Bloom A, Bot A. Noncoding RNA danger motifs bridge innate and adaptive immunity and are potent adjuvants for vaccination. J Clin Invest 2002; 110 (08) 1175-1184
- 111 Kimura T, Tse K, McArdle S. , et al. Atheroprotective vaccination with MHC-II-restricted ApoB peptides induces peritoneal IL-10-producing CD4 T cells. Am J Physiol Heart Circ Physiol 2017; 312 (04) H781-H790
- 112 Elion DL, Cook RS. Harnessing RIG-I and intrinsic immunity in the tumor microenvironment for therapeutic cancer treatment. Oncotarget 2018; 9 (48) 29007-29017
- 113 Asdonk T, Steinmetz M, Krogmann A. , et al. MDA-5 activation by cytoplasmic double-stranded RNA impairs endothelial function and aggravates atherosclerosis. J Cell Mol Med 2016; 20 (09) 1696-1705
- 114 Ramachandran B, Stabley JN, Cheng SL. , et al. A GTPase-activating protein-binding protein (G3BP1)/antiviral protein relay conveys arteriosclerotic Wnt signals in aortic smooth muscle cells. J Biol Chem 2018; 293 (21) 7942-7968
- 115 Christ A, Bekkering S, Latz E, Riksen NP. Long-term activation of the innate immune system in atherosclerosis. Semin Immunol 2016; 28 (04) 384-393
- 116 Wolf D, Ley K. Immunity and inflammation in atherosclerosis. Circ Res 2019; 124 (02) 315-327
- 117 Li X, Liu CX, Xue W. , et al. Coordinated circRNA biogenesis and function with NF90/NF110 in viral infection. Mol Cell 2017; 67 (02) 214-227
- 118 Hochheiser K, Klein M, Gottschalk C. , et al. Cutting edge: the RIG-I ligand 3pRNA potently improves CTL cross-priming and facilitates antiviral vaccination. J Immunol 2016; 196 (06) 2439-2443
- 119 Visel A, Zhu Y, May D. , et al. Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nature 2010; 464 (7287): 409-412
- 120 Ulitsky I. Evolution to the rescue: using comparative genomics to understand long non-coding RNAs. Nat Rev Genet 2016; 17 (10) 601-614
- 121 Kim DY, Atasheva S, McAuley AJ. , et al. Enhancement of protein expression by alphavirus replicons by designing self-replicating subgenomic RNAs. Proc Natl Acad Sci U S A 2014; 111 (29) 10708-10713
- 122 Bester AC, Lee JD, Chavez A. , et al. An integrated genome-wide CRISPRa approach to functionalize lncRNAs in drug resistance. Cell 2018; 173 (03) 649-664
- 123 Müller S, Appel B. In vitro circularization of RNA. RNA Biol 2017; 14 (08) 1018-1027
- 124 Suzuki H, Ando T, Umekage S, Tanaka T, Kikuchi Y. Extracellular production of an RNA aptamer by ribonuclease-free marine bacteria harboring engineered plasmids: a proposal for industrial RNA drug production. Appl Environ Microbiol 2010; 76 (03) 786-793
- 125 Chen T, Romesberg FE. Polymerase chain transcription: exponential synthesis of RNA and modified RNA. J Am Chem Soc 2017; 139 (29) 9949-9954
- 126 Baronti L, Karlsson H, Marušič M, Petzold K. A guide to large-scale RNA sample preparation. Anal Bioanal Chem 2018; 410 (14) 3239-3252
- 127 Abudayyeh OO, Gootenberg JS, Essletzbichler P. , et al. RNA targeting with CRISPR-Cas13. Nature 2017; 550 (7675): 280-284
- 128 Cox DBT, Gootenberg JS, Abudayyeh OO. , et al. RNA editing with CRISPR-Cas13. Science 2017; 358 (6366): 1019-1027
- 129 Khvorova A, Watts JK. The chemical evolution of oligonucleotide therapies of clinical utility. Nat Biotechnol 2017; 35 (03) 238-248
- 130 Wang Y, Li Y, Toth JI, Petroski MD, Zhang Z, Zhao JC. N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells. Nat Cell Biol 2014; 16 (02) 191-198
- 131 Liu N, Dai Q, Zheng G, He C, Parisien M, Pan T. N(6)-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature 2015; 518 (7540): 560-564
- 132 Patil DP, Chen CK, Pickering BF. , et al. m(6)A RNA methylation promotes XIST-mediated transcriptional repression. Nature 2016; 537 (7620): 369-373
- 133 Kasowitz SD, Ma J, Anderson SJ. , et al. Nuclear m6A reader YTHDC1 regulates alternative polyadenylation and splicing during mouse oocyte development. PLoS Genet 2018; 14 (05) e1007412
- 134 Rueter SM, Dawson TR, Emeson RB. Regulation of alternative splicing by RNA editing. Nature 1999; 399 (6731): 75-80
- 135 Davis DR. Stabilization of RNA stacking by pseudouridine. Nucleic Acids Res 1995; 23 (24) 5020-5026
- 136 Karijolich J, Yu YT. Converting nonsense codons into sense codons by targeted pseudouridylation. Nature 2011; 474 (7351): 395-398
- 137 Kawahara Y, Zinshteyn B, Sethupathy P, Iizasa H, Hatzigeorgiou AG, Nishikura K. Redirection of silencing targets by adenosine-to-inosine editing of miRNAs. Science 2007; 315 (5815): 1137-1140
- 138 Goldstein B, Agranat-Tamir L, Light D, Ben-Naim Zgayer O, Fishman A, Lamm AT. A-to-I RNA editing promotes developmental stage-specific gene and lncRNA expression. Genome Res 2017; 27 (03) 462-470
- 139 Smola MJ, Weeks KM. In-cell RNA structure probing with SHAPE-MaP. Nat Protoc 2018; 13 (06) 1181-1195
- 140 Kashi K, Henderson L, Bonetti A, Carninci P. Discovery and functional analysis of lncRNAs: methodologies to investigate an uncharacterized transcriptome. Biochim Biophys Acta 2016; 1859 (01) 3-15
- 141 Kamaly N, Fredman G, Subramanian M. , et al. Development and in vivo efficacy of targeted polymeric inflammation-resolving nanoparticles. Proc Natl Acad Sci U S A 2013; 110 (16) 6506-6511
- 142 Duivenvoorden R, Tang J, Cormode DP. , et al. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation. Nat Commun 2014; 5: 3065
- 143 Zhang Y, Yu J, Kahkoska AR, Gu Z. Photoacoustic drug delivery. Sensors (Basel) 2017; 17 (06) E1400
- 144 Lubbe AS, Szymanski W, Feringa BL. Recent developments in reversible photoregulation of oligonucleotide structure and function. Chem Soc Rev 2017; 46 (04) 1052-1079
- 145 Kaczmarek JC, Kowalski PS, Anderson DG. Advances in the delivery of RNA therapeutics: from concept to clinical reality. Genome Med 2017; 9 (01) 60
- 146 Cole JE, Park I, Ahern DJ. , et al. Immune cell census in murine atherosclerosis: cytometry by time of flight illuminates vascular myeloid cell diversity. Cardiovasc Res 2018; 114 (10) 1360-1371
- 147 Misra A, Feng Z, Chandran RR. , et al. Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells. Nat Commun 2018; 9 (01) 2073
- 148 Guimarães-Camboa N, Evans SM. Are perivascular adipocyte progenitors mural cells or adventitial fibroblasts?. Cell Stem Cell 2017; 20 (05) 587-589
- 149 Cusanovich DA, Hill AJ, Aghamirzaie D. , et al. A single-cell atlas of in vivo mammalian chromatin accessibility. Cell 2018; 174 (05) 1309-1324