Date of download: 11/11/2016 Copyright © The American College of Cardiology. All rights reserved. From: Long Noncoding RNAs: From Clinical Genetics to Therapeutic Targets? J Am Coll Cardiol. 2016;67(10): doi: /j.jacc Figure Legend: The RNA World and Cardiovascular Disease: Long Noncoding RNAs Depending on the subcellular localization, long noncoding RNAs (lncRNAs) can act via various mechanisms. By mimicking transcription factor binding sites, double-stranded regions of lncRNAs can bind to transcription factors, thereby functioning as a decoy. Via binding to chromatin modifiers, lncRNAs contribute to epigenetic silencing or activation of gene expression. LncRNAs that bind to exon/intron junctions of pre– messenger RNA (mRNA) can influence (alternative) splicing. Several lncRNAs act as a scaffold in ribonucleoprotein (RNP) complexes. In the cytoplasm, numerous lncRNAs have been shown to bind microRNAs (miRNAs), thereby preventing the miRNAs from binding to and regulating their mRNA targets. By masking binding sites for proteins or miRNAs, cytoplasmic lncRNAs can alter the stability of mRNAs.

Date of download: 11/11/2016 Copyright © The American College of Cardiology. All rights reserved. From: Long Noncoding RNAs: From Clinical Genetics to Therapeutic Targets? J Am Coll Cardiol. 2016;67(10): doi: /j.jacc Figure Legend: Noncoding RNAs of the Human Transcriptome The human genome is nearly pervasively transcribed, resulting in an almost noncoding transcriptome with various RNA species. ∗ Depicted RNA classification does not rely on a strict 200 nt cutoff. H1 RNA = RNA component of ribonuclease P; miRNAs = microRNAs; mRNA = messenger RNA; mtRNA = mitochondrial RNA; piRNAs = piwi-interacting RNAs; RMRP = RNA component of RNase MRP; rRNA = ribosomal RNA; scaRNAs = small Cajal body-specific RNAs; 7SL RNA = signal recognition particle RNA; snoRNAs = small nucleolar RNAs; snRNAs = small nuclear RNAs; TERC = telomerase RNA component; tRNAs = transfer RNAs; Y RNAs = part of the RoRNP.

Date of download: 11/11/2016 Copyright © The American College of Cardiology. All rights reserved. From: Long Noncoding RNAs: From Clinical Genetics to Therapeutic Targets? J Am Coll Cardiol. 2016;67(10): doi: /j.jacc Figure Legend: Long Noncoding RNAs Regulate Vascular Function (A) The long noncoding RNAs (lncRNAs) myocardial infarction-associated transcript (MIAT) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) have been implicated in angiogenesis and inflammation in diabetic retinopathy. Both lncRNAs are up-regulated in diabetic retinopathy and affect endothelial cell function. MALAT1 is also induced by hypoxia. Linc and MIR503HG are both induced by hypoxia and regulate endothelial proliferation and migration via GATA2. (B) The lncRNA RP5-833A20.1 was reported to control cholesterol homeostasis, with potential implications for atherosclerosis. Antisense noncoding RNA in the INK4 locus (ANRIL), smooth muscle and endothelial cell-enriched migration/differentiation-associated long noncoding RNA (SENCR), and linc-p21 were shown to be involved in phenotypic control of cells in the vascular wall. HDL = high-density lipoprotein; LDL = low-density lipoprotein; NFIA = nuclear factor IA; PRC1/2 = PRC1, polycomb repressive complex 1/2.

Date of download: 11/11/2016 Copyright © The American College of Cardiology. All rights reserved. From: Long Noncoding RNAs: From Clinical Genetics to Therapeutic Targets? J Am Coll Cardiol. 2016;67(10): doi: /j.jacc Figure Legend: Long Noncoding RNAs Regulate Cardiac Function Several long noncoding RNAs (lncRNAs) were shown to regulate cardiac physiology. Cardiac-apoptosis related long noncoding ribonucleic acid (CARL), mitochondrial dynamic related long noncoding ribonucleic acid (MDRL), and autophagy-promoting factor (APF) regulate cardiomyocyte cell death by inhibiting microRNAs. Cardiac hypertrophy related factor (CHRF) also functions as a microRNA sponge in the context of cardiac hypertrophy and inhibits miR-489. The lncRNA myosin heavy chain-associated ribonucleic acid transcript (Mhrt) regulates chromatin remodeling and cardiac hypertrophy. Novlnc6 is involved in cardiac development.