Landscape of the long non-coding RNA transcriptome in human heart

Long non-coding RNAs (lncRNAs) have been revealed to play essential roles in the human cardiovascular system. However, information about their mechanisms is limited, and a comprehensive view of cardiac lncRNAs is lacking from a multiple tissues perspective to date. Here, the landscape of the lncRNA transcriptome in human heart was summarized. We summarized all lncRNA transcripts from publicly available human transcriptome resources (156 heart samples and 210 samples from 29 other tissues) and systematically analysed all annotated and novel lncRNAs expressed in heart. A total of 7485 lncRNAs whose expression was elevated in heart (HE lncRNAs) and 453 lncRNAs expressed in all 30 analysed tissues (EIA lncRNAs) were extracted. Using various bioinformatics resources, methods and tools, the features of these lncRNAs were discussed from various perspectives, including genomic structure, conservation, dynamic variation during heart development, cis-regulation, differential expression in cardiovascular diseases and cancers as well as regulation at transcriptional and post-transcriptional levels. Afterwards, all the features discussed above were integrated into a user-friendly resource named CARDIO-LNCRNAS (http://bio-bigdata.hrbmu.edu.cn/CARDIO-LNCRNAS/ or http://www.bio-bigdata.net/CARDIO-LNCRNAS/). This study represents the first global view of lncRNAs in the human cardiovascular system based on multiple tissues and sheds light on the role of lncRNAs in developments and heart disorders.

[1]  Helen M. Moore,et al.  Acknowledgement to Reviewers of the Journal of Personalized Medicine in 2013 , 2014, Journal of Personalized Medicine.

[2]  Linda Szabo,et al.  Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development , 2015, Genome Biology.

[3]  E. Zaklyazminskaya,et al.  Cardiac channelopathies: genetic and molecular mechanisms. , 2013, Gene.

[4]  D. Haussler,et al.  Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. , 2005, Genome research.

[5]  E. Levanon,et al.  Human housekeeping genes are compact. , 2003, Trends in genetics : TIG.

[6]  S. Dhanasekaran,et al.  The landscape of long noncoding RNAs in the human transcriptome , 2015, Nature Genetics.

[7]  David R. Kelley,et al.  Transposable elements reveal a stem cell-specific class of long noncoding RNAs , 2012, Genome Biology.

[8]  Cole Trapnell,et al.  Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. , 2011, Genes & development.

[9]  Jeannie T. Lee.  Epigenetic Regulation by Long Noncoding RNAs , 2012, Science.

[10]  G. Bejerano,et al.  Coding exons function as tissue-specific enhancers of nearby genes , 2012, Genome research.

[11]  S. Dimmeler,et al.  Long Noncoding RNAs in Cardiovascular Diseases , 2015, Circulation research.

[12]  A. Schambach,et al.  Long noncoding RNA Chast promotes cardiac remodeling , 2016, Science Translational Medicine.

[13]  Michael F. Lin,et al.  Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals , 2009, Nature.

[14]  Walter Birchmeier,et al.  Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy , 2004, Nature Genetics.

[15]  Anjali J. Koppal,et al.  Supplementary data: Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites , 2010 .

[16]  Carlos L Arteaga,et al.  Cardio-Oncology: How New Targeted Cancer Therapies and Precision Medicine Can Inform Cardiovascular Discovery. , 2015, Circulation.

[17]  C. Ponting,et al.  Evolution and Functions of Long Noncoding RNAs , 2009, Cell.

[18]  Piero Carninci,et al.  Transcriptome Analysis of Recurrently Deregulated Genes across Multiple Cancers Identifies New Pan-Cancer Biomarkers. , 2016, Cancer research.

[19]  Eun Ji Kim,et al.  Simulation-based comprehensive benchmarking of RNA-seq aligners , 2016, Nature Methods.

[20]  Masaharu Kataoka,et al.  Non-Coding RNAs Including miRNAs and lncRNAs in Cardiovascular Biology and Disease , 2014, Cells.

[21]  Vincent L. Butty,et al.  Braveheart, a Long Noncoding RNA Required for Cardiovascular Lineage Commitment , 2013, Cell.

[22]  T. Derrien,et al.  Long Noncoding RNAs with Enhancer-like Function in Human Cells , 2010, Cell.

[23]  Toshihiro Tamura,et al.  Increased MicroRNA-1 and MicroRNA-133a Levels in Serum of Patients With Cardiovascular Disease Indicate Myocardial Damage , 2011, Circulation. Cardiovascular genetics.

[24]  Michael F. Clarke,et al.  Downregulation of miRNA-200c Links Breast Cancer Stem Cells with Normal Stem Cells , 2009, Cell.

[25]  Thomas J. Ha,et al.  Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells , 2015, Science.

[26]  Linda Koch,et al.  Cancer genomics: A catalogue of somatic mutations , 2016, Nature Reviews Genetics.

[27]  Zheng Zhao,et al.  Identifying and functionally characterizing tissue-specific and ubiquitously expressed human lncRNAs , 2016, Oncotarget.

[28]  William R. Bauer.  DNA Structure and Function.Richard R. Sinden , 1995 .

[29]  G. Ewald,et al.  Deep RNA Sequencing Reveals Dynamic Regulation of Myocardial Noncoding RNAs in Failing Human Heart and Remodeling With Mechanical Circulatory Support , 2014, Circulation.

[30]  Ming Liu,et al.  Integrated Analysis of Dysregulated lncRNA Expression in Fetal Cardiac Tissues with Ventricular Septal Defect , 2013, PloS one.

[31]  A. Gylfason,et al.  A Common Variant on Chromosome 9p21 Affects the Risk of Myocardial Infarction , 2007, Science.

[32]  D. Bartel,et al.  lincRNAs: Genomics, Evolution, and Mechanisms , 2013, Cell.

[33]  J. Trowsdale,et al.  Genomic structure and function in the MHC. , 1993, Trends in genetics : TIG.

[34]  Daniela Hoeller,et al.  Ubiquitin and ubiquitin-like proteins in cancer pathogenesis , 2006, Nature Reviews Cancer.

[35]  Ralf Herwig,et al.  ConsensusPathDB—a database for integrating human functional interaction networks , 2008, Nucleic Acids Res..

[36]  J. Mattick,et al.  Long non-coding RNAs: insights into functions , 2009, Nature Reviews Genetics.

[37]  Zev N. Kronenberg,et al.  Transposable Elements Are Major Contributors to the Origin, Diversification, and Regulation of Vertebrate Long Noncoding RNAs , 2013, PLoS genetics.

[38]  Thomas H Marwick,et al.  Cancer Therapy-Related Cardiac Dysfunction: Unresolved Issues. , 2016, The Canadian journal of cardiology.

[39]  James T. Elder,et al.  Analysis of long non-coding RNAs highlights tissue-specific expression patterns and epigenetic profiles in normal and psoriatic skin , 2015, Genome Biology.

[40]  Wing Hung Wong,et al.  Gaining comprehensive biological insight into the transcriptome by performing a broad-spectrum RNA-seq analysis , 2017, Nature Communications.

[41]  Yong Cai,et al.  A potential diagnostic marker for ovarian cancer: Involvement of the histone acetyltransferase, human males absent on the first , 2013, Oncology letters.

[42]  Mark D. Robinson,et al.  edgeR: a Bioconductor package for differential expression analysis of digital gene expression data , 2009, Bioinform..

[43]  G. von Heijne,et al.  Tissue-based map of the human proteome , 2015, Science.

[44]  David John,et al.  The identification and characterization of novel transcripts from RNA-seq data , 2016, Briefings Bioinform..

[45]  Jia Yu,et al.  miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. , 2010, Cancer research.

[46]  Dmitri D. Pervouchine,et al.  The human transcriptome across tissues and individuals , 2015, Science.

[47]  Steven J. M. Jones,et al.  Circos: an information aesthetic for comparative genomics. , 2009, Genome research.

[48]  Christopher R. Cabanski,et al.  Transcriptome sequencing reveals altered long intergenic non-coding RNAs in lung cancer , 2014, Genome Biology.

[49]  B. Chowchuen,et al.  Prevalence of Congenital Heart Diseases in Patients with Orofacial Clefts: A Systematic Review. , 2015, Journal of the Medical Association of Thailand = Chotmaihet thangphaet.

[50]  Sherry-Ann Brown,et al.  Systems biology approaches to adverse drug effects: the example of cardio-oncology , 2015, Nature Reviews Clinical Oncology.

[51]  David G. Knowles,et al.  The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression , 2012, Genome research.

[52]  F. Liu,et al.  The Long Noncoding RNA CHRF Regulates Cardiac Hypertrophy by Targeting miR-489 , 2014, Circulation research.

[53]  B. Qian,et al.  Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia , 2012, Nature Genetics.

[54]  Mingming Jia,et al.  COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer , 2010, Nucleic Acids Res..

[55]  Eoin Fahy,et al.  MitoProteome: mitochondrial protein sequence database and annotation system , 2004, Nucleic Acids Res..

[56]  G Opelz,et al.  The influence of HLA compatibility on graft survival after heart transplantation. The Collaborative Transplant Study. , 1994, The New England journal of medicine.

[57]  Manel Esteller,et al.  Cis-acting noncoding RNAs: friends and foes , 2012, Nature Structural &Molecular Biology.

[58]  Frank Grützner,et al.  The evolution of lncRNA repertoires and expression patterns in tetrapods , 2014, Nature.

[59]  Suleyman Bilgin,et al.  ARİTMİK EKG SİNYALLERİNDE DAYANIKLI YENİ BİR QRS YAKALAMA ALGORİTMASI , 2018 .

[60]  Yusuke Nakamura,et al.  Identification of a novel non-coding RNA, MIAT, that confers risk of myocardial infarction , 2006, Journal of Human Genetics.

[61]  Peggy Hall,et al.  The NHGRI GWAS Catalog, a curated resource of SNP-trait associations , 2013, Nucleic Acids Res..

[62]  S. Dimmeler,et al.  Long Noncoding RNA MALAT1 Regulates Endothelial Cell Function and Vessel Growth , 2014, Circulation Research.

[63]  Zahide Elif Akin,et al.  A NEW ROBUST QRS DETECTION ALGORITHM IN ARRHYTHMIC ECG SIGNALS , 2018 .

[64]  J. Dausset,et al.  Implication of HLA-G molecule in heart-graft acceptance , 2000, The Lancet.

[65]  A. Stark,et al.  Transcriptional enhancers: from properties to genome-wide predictions , 2014, Nature Reviews Genetics.

[66]  Jens Nielsen,et al.  Transcriptomics resources of human tissues and organs , 2016, Molecular systems biology.

[67]  Manolis Kellis,et al.  Evolutionary dynamics and tissue specificity of human long noncoding RNAs in six mammals , 2014, Genome research.

[68]  Cole Trapnell,et al.  TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions , 2013, Genome Biology.

[69]  Jun Yu,et al.  MTD: a mammalian transcriptomic database to explore gene expression and regulation , 2016, Briefings Bioinform..

[70]  Howard Y. Chang,et al.  Unique features of long non-coding RNA biogenesis and function , 2015, Nature Reviews Genetics.

[71]  Julien Mairal,et al.  Efficient RNA isoform identification and quantification from RNA-Seq data with network flows , 2014, Bioinform..

[72]  Rama Natarajan,et al.  Noncoding RNAs in vascular disease , 2014, Current opinion in cardiology.

[73]  Min Pan,et al.  A miRNA-regulatory network explains how dysregulated miRNAs perturb oncogenic processes across diverse cancers , 2012, Genome research.

[74]  Bridget E. Begg,et al.  A Proteome-Scale Map of the Human Interactome Network , 2014, Cell.

[75]  David R. Kelley,et al.  Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks , 2012, Nature Protocols.

[76]  Dimitris Tousoulis,et al.  Biomarkers in Aortic Valve Stenosis and their Clinical Significance in Transcatheter Aortic Valve Implantation. , 2019, Current medicinal chemistry.

[77]  Jun Yu,et al.  LncRNAWiki: harnessing community knowledge in collaborative curation of human long non-coding RNAs , 2014, Nucleic Acids Res..

[78]  Stephane Heymans,et al.  Circulating MicroRNA-208 b and MicroRNA-499 Reflect Myocardial Damage in Cardiovascular Disease Running title : , 2010 .

[79]  E. Levanon,et al.  Human housekeeping genes, revisited. , 2013, Trends in genetics : TIG.

[80]  T. Meehan,et al.  An atlas of active enhancers across human cell types and tissues , 2014, Nature.

[81]  Thomas Thum,et al.  Non-coding RNAs in cardiac remodeling and heart failure. , 2013, Circulation research.

[82]  J. Mattick,et al.  Long Noncoding RNAs in Cardiac Development and Pathophysiology , 2012, Circulation research.

[83]  J. Kocher,et al.  CPAT: Coding-Potential Assessment Tool using an alignment-free logistic regression model , 2013, Nucleic acids research.

[84]  A. Feinberg,et al.  Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA , 2008, Nature.

[85]  M. McCarthy,et al.  Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes. , 2012, Cell metabolism.

[86]  C. Berul,et al.  An Update on Channelopathies: From Mechanisms to Management , 2013, Circulation.

[87]  Zhuo Xi,et al.  Role of HCP5-miR-139-RUNX1 Feedback Loop in Regulating Malignant Behavior of Glioma Cells. , 2016, Molecular therapy : the journal of the American Society of Gene Therapy.

[88]  Ying Cheng,et al.  The European Nucleotide Archive , 2010, Nucleic Acids Res..

[89]  R. Sandberg,et al.  Genome-wide mapping of promoter-anchored interactions with close to single-enhancer resolution , 2015, Genome Biology.

[90]  Hui Zhou,et al.  starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein–RNA interaction networks from large-scale CLIP-Seq data , 2013, Nucleic Acids Res..