Human lncrnas participate in a spectrum of biological processes, for example, epigenetics, nuclear import, alternative splicing, rna decay and translation 2. Long noncoding rnas during normal and malignant hematopoiesis long noncoding rnas during normal and malignant hematopoiesis. Here, we developed a heart disease related noncoding rnas database hdncrna, to curate the hdsncrna associations from 3 different sources including 1904 published articles, 3 existing databases the human microrna disease database hmdd, mir2disease and lncrnadisease and 5 rnaseq datasets. Functional demarcation of active and silent chromatin domains in human hox loci by noncoding rnas author links open overlay panel john l. Noncoding dna sequences are components of an organisms dna that do not encode protein sequences. Circular rnas circrnas, a class of widespread endogenous rnas, play crucial roles in diverse biological processes and are potential biomarkers in diverse human diseases and cancers. Frontiers noncoding rnas in human saliva as potential. Here we demonstrate genomewide screening of lncrna function. Long noncoding rnas at the heart of development and disease. Previous studies have shown that functional noncoding regions in the human genome had conserved rna secondary structures, 44 and certain human diseases could be caused by variants inducing structural changes, 28 suggesting rna structural change as a potential molecular cause of the disease. Some noncoding dna is transcribed into functional noncoding rna molecules e. Meet some codebreakers of noncoding rnas nature methods. In a single issue of genes in spring of 2017, we would like to focus on the roles of micrornas and long noncoding rnas in human diseases, highlighting what is already known about their function and describing the challenges for the near future development of biomarkers and new therapeutics. Boone, phd1,2, 1university of pittsburgh, department of biomedical informatics 2computer science, biology, and biomedical informatics and university of pittsburgh cancer institute academies 3university of pittsburgh, chemistry department abstract.
For 50 years the term gene has been synonymous with regions of the genome encoding mrnas that are translated into protein. Here we discuss examples where mutation in classical noncoding rnas have been attributed to human disease and identify the future potential for the noncoding portion of the genome in disease biology. Importantly, an increasing number of lncrnas have also been associated with a range of human diseases, including cancer. The role of long noncoding rnas in hepatocellular carcinoma. Long noncoding rnas lncrnas are emerging as important regulators of tissue physiology and disease processes including cancer. The functional relevance of the nonproteincoding genome is particularly evident for a class of small noncoding rnas ncrnas called micrornas mirnas3,4.
Jci targeting noncoding rnas in disease journal of clinical. Chang howard hughes medical institute and program in epithelial biology, stanford, ca 94305, usa a new class of transcripts, long noncoding rnas lncrnas, has been recently found to be pervasively transcribed in the genome. Long noncoding rnas and human disease orly wapinski and howard y. Taft rj1, pang kc, mercer tr, dinger m, mattick js. A comprehensive collection of 270,044 human lncrnas and systematic curation of lncrnas annotation by multiomics data integration, function annotation and disease association. The functional role of long noncoding rna in human carcinomas the functional role of long noncoding rna in human carcinomas. The relevance of the noncoding genome to human disease has mainly been studied in the context of the widespread disruption of microrna mirna expression and function that is seen in human cancer. Lnctar runs fast and therefore can be used for largescale identification of the rna targets for long noncoding rnas. While most of the focus is on mirnas as small noncoding rnas, other long or small noncoding rnas are attracting attention in normal and in cancer cells. Whole genome profiling of mrnas from a common tissue source has been employed to analyze an array of diseases, including autoimmune diseases. Request pdf noncoding rnas in human diseases the relevance of the noncoding genome to human disease has mainly been studied in the context of the. Mechanisms of long noncoding rna function in development and disease mechanisms of long noncoding rna function in development and disease.
A global map for dissecting phenotypic variants in human. Special issue the role of noncoding rnas in human lung health and disease print special issue flyer. Long noncoding rnas and human disease sciencedirect. There is a growing number of genes which yield noncoding rnas ncrna playing multiple functions in regulation of gene expression. The continued improvement of innovative rna modifications and delivery entities, such as nanoparticles, will aid in the development of future rnabased therapeutics for a broader range of chronic diseases. The targeting of these hallmarks with noncoding rnas can affect vital metabolic and cell signaling pathways, which as a result can potentially have a role in cancerous and pathological processes. Long noncoding rnas expression in human diseases as described above, the wide diversity of human lncrnas is consistent with their diverse roles in gene expression. The functions of many long noncoding rnas lncrnas in the human genome remain unknown owing to the lack of scalable lossoffunction screening tools. Deep rna sequencing uncovers a repertoire of human. Insights from global analyses of long noncoding rnas in breast cancer andrew j. The lncrna hox transcript antisense rna hotair is a prime example of an oncogenic transacting lncrna. Lnctar does not have limit to rna size, indicating lnctar can be used to all rnas. Functional demarcation of active and silent chromatin.
Identification of long noncoding rnas associated to human. Noncoding rnas act as a chromatin scaffold of histone modification complexes in cancer 19. Although a number of circrnas have been identified by bioinformatics analysis of rnaseq data, tissue and disease specific circrnas are still to be uncovered to promote their application in basic research and clinical practice. Insights from global analyses of long noncoding rnas in. In human diseases, particularly cancer, it has been shown that epigenetic and genetic. Long noncoding rnas lncrnas represent one of the largest classes of transcripts and are highly diverse in terms of characteristics and functions. The relevance of the noncoding genome to human disease has mainly been studied in the context of the widespread disruption of microrna. A new class of transcripts, long noncoding rnas lncrnas, has been recently found to be pervasively transcribed in the genome. Functions of long noncoding rnas in human disease and their. The role of long noncoding rna in major human disease.
Our results found that some known disease associated. The purpose of this study was to explore the circrna profiles in human induced. The role of long noncoding rnas in regulating invasion and. To delineate genomewide lncrna expression, we curated 7,256 rna. Long intergenic noncoding rnas lincrnas lincrnacox210 and lincrnaeps11 have been shown to be critical regulators of in. Circular rnas circrnas are regarded as a novel class of noncoding rna regulators. Choose species and type, then browse all the entries. However, we are only beginning to understand the nature and extent of the involvement of noncoding rnas ncrnas in disease. Special issue the role of noncoding rnas in human lung. Cross talk between noncoding rnas and dna methylation and demethylation in cancer 18. Long noncoding rnas long ncrnas, lncrna are a type of rna, defined as being transcripts with lengths exceeding 200 nucleotides that are not translated into protein. Multiple lines of evidence increasingly link mutations and dysregulations of. Other functions of noncoding dna include the transcriptional and translational regulation of proteincoding sequences, scaffold attachment regions, origins of dna. Multiple lines of evidence increasingly link mutations and dysregulations of lncrnas to diverse human diseases.
Elucidating the functional roles of noncoding rnas in viral infectious diseases r21. Accumulating researches have linked dysregulations and mutations of lncrnas to a variety of human disorders and diseases. Alterations in the primary structure, secondary structure, and expression levels of lncrnas as well as their cognate rnabinding proteins underlie diseases. For some lncrnas the connection with human diseases was made through gwas genome wide association studies or investigating differential. Basic science, human translational research studies and therapeutic development projects will be welcomed. A wikibased, publicly editable and opencontent platform for community curation of human long noncoding rnas lncrnas lncbook. A noncoding rna ncrna is an rna molecule that is not translated into a protein. This somewhat arbitrary limit distinguishes long ncrnas from small noncoding rnas such as micrornas mirnas, small interfering rnas sirnas, piwiinteracting rnas pirnas, small nucleolar rnas snornas, and other short rnas. We now appreciate that the majority of the human genome is transcribed and many new rna classes, such as long noncoding rnas lncrnas, enhancerassociated rnas, micro rnas and piwiinteracting rnas have been identified 24. Special issue micrornas and other noncoding rnas in. Advances in highthroughput sequencing platforms have enabled the rapid discovery and identification of lncrnas as key regulatory molecules involved in various cellular processes and their dysregulation in various human diseases.
Noncoding rnas in human saliva as potential disease biomarkers xianzhi lin 1, hsienchun lo 1, david t. Here we summarize the latest promises and challenges of targeting noncoding rnas in disease. The role of long noncoding rnas in the pathogenesis of hereditary. Signature of circular rnas in human induced pluripotent. Functional characterization of long noncoding rnas. Although few lncrnas have been the subject of detailed molecular and functional characterization, it is believed that lncrnas play an. By further understanding noncoding rnas, researchers can work towards diagnoses and treatments to improve early detection and clinical response.
However, to date, only a few human lncrnas have been associated with diseases. Using our lncrna pipeline, we identify pinky pnky as a long noncoding rna lncrna that regulates the transition between nscs and neurogenic progenitors. Pnky is expressed in nsc populations and becomes downregulated during neurogenesis. Review open access the role of long noncoding rnas in hepatocellular carcinoma zhao huang1, jiankang zhou1, yong peng1, weifeng he2 and canhua huang1 abstract hepatocellular carcinoma hcc is the most frequent subtype of primary liver cancer and one of the leading causes. Noncoding rnas in human diseases request pdf researchgate. Furthermore, it is increasingly recognized that mutation and dysregulation of lncrnas contribute importantly to a variety of human diseases, particularly human cancers.
This volume focuses on the roles of long noncoding rnas lncrnas in contexts ranging from human cancers to cardiovascular disease and ageing. Expression of long noncoding rnas in autoimmunity and. Request pdf noncoding rnas in human diseases the relevance of the non coding genome to human disease has mainly been studied in the context of the. Physiological roles of noncoding rnas american physiological.
In parallel, a rapidly growing number of studies has unravelled associations between aberrant noncoding rna expression and human diseases. Pdf the mechanism and function of circular rnas in human. Here we provide an overview of currently known noncoding rna elements figure 1, their functions, and their connections with disease states. Nih funding opportunities and notices in the nih guide for grants and contracts. Long noncoding rnas lncrnas have emerged as a new family of master regulators of cancer.
Long non coding rnas lncrnas are subpopulation of transcriptome that has crucial activity in cells and also molecular pathways. In human diseases, particularly cancer, it has been shown that epigenetic and genetic defects in mirnas and their processing machinery are a common hallmark of disease58. Long noncoding rnas lncrnas are a group of nonproteincoding transcripts exceeding 200 nucleotides in length, which are emerging as key players in various fundamental biological processes. Role of long noncoding rnas in normal and malignant. As a major class of noncoding rnas, long noncoding rnas lncrnas have been implicated in various critical biological processes. All known ncrnas may be divided into two groups, namely. Genomewide screening for functional long noncoding rnas. Noncoding rnas in cardiovascular diseases pp 3148 cite as.
The dna sequence from which a functional noncoding rna is transcribed is often called an rna gene. Noncoding rna s are emerging as potent and multifunctional regulators in all biological processes. Noncoding rnas as epigenetic gene regulators in cardiovascular diseases. Alterations in the primary structure, secondary structure, and.
A genomic profiling tcga study showed that in approximately 5,000 tumor samples, although approximately the same number of proteincoding genes and lncrna genes were disordered, 60% of the lncrnas showed specificity for only one tumor type. Many of the ncrnas have been shown to be associated with certain human diseases including neurobehavioral, developmental disorders and cancer. Heterochromatin modulation and pcg control of gene expression medicated by noncoding rna in cancer 20. Accord ing to the latest annotations of human genes at the ensembl.
With the completion of large scale genomic sequencing, a great number of nonconding rnas ncrnas have been discovered and capture the attention of the biological sciences community. Minisymposium long noncoding rnas at the heart of development and disease centre hospitalier universitaire vaudois chuv lausanne16 september, 2016. Abstract the relevance of the noncoding genome to human disease has mainly been. Autoimmune diseases as immune system dysregulation have been. We presented a method and developed a tool, lnctar, to predict the rna targets of long noncoding rnas. Request pdf identification of long noncoding rnas associated to human disease susceptibility transcriptomic as well as in vivo studies have revealed the importance of several lncrnas in many.
1061 1258 98 291 848 696 790 1038 1614 161 902 794 543 321 166 923 1530 449 758 639 631 1202 934 1171 159 855 1066 1115 1135