Moreover, they appear as new promising noninvasive biomarkers for early lung cancer diagnosis. Insights from global analyses of long noncoding rnas in breast cancer andrew j. 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. Exosomal long noncoding rnas as biomarkers in human. Noncoding rnas are not translated into proteins and have emerged as fundamental regulators of gene expression. In the last decade we just started to realize the biologic function and complexity of gene regulation by small noncoding rnas. Recent studies reported that micrornas and long noncoding rnas are involved in lung cancer development and progression. The role of long noncoding rna in major human disease. Long noncoding rnas lncrnas are longer than 200 nucleotide and lack proteincoding potential. To delineate genomewide lncrna expression, we curated 7,256 rna sequencing rnaseq libraries from tumors, normal tissues and cell lines comprising over 43 tb of sequence from 25 independent studies.
Long noncoding rnas and human disease sciencedirect. Pdf for 50 years the term gene has been synonymous with regions of the genome encoding mrnas that are translated into protein. Novel aspects of trnaderived small rnas with potential. Long noncoding rnas lncrnas represent one of the largest classes of transcripts and are highly diverse in terms of characteristics and functions.
A comprehensive collection of 270,044 human lncrnas and systematic curation of lncrnas annotation by multiomics data integration, function annotation and disease association. Long noncoding rnas expressed in human hepatic stellate cells form networks with extracellular matrix proteins chan zhou, samuel r. Pdf osteosarcoma is the most commonly diagnosed malignancies in children and adolescents, pathologically characterized by spindle cells and deviant. Here we show that this mechanism regulates tumorigenesis in human cells, with human rnas replacing vl301 rna. Long noncoding and coding rnas characterization in. The research progress of long noncoding rnas in autoimmune diseases li zou, md rezaul karim and yunfu wang department of neurology, t aihe hospital, hubei university of medicine, shiyan, hubei. Functional annotation of structural ncrnas within enhancer. In human diseases, particularly cancer, it has been shown that epigenetic and genetic. Noncoding rnas in cell fate determination public summary.
Rna biology provides new therapeutic targets for human disease. Discovering putative peptides encoded from noncoding rnas. Long noncoding rnas and human disease orly wapinski and howard y. Aberrant epigenetic modifications of noncoding rnas in. The landscape of long noncoding rnas in the human transcriptome.
Noncoding rnas ncrnas are classes of transcripts that are encoded by the genome and transcribed but never get translated into proteins. Noncoding rnas, a group of ribonucleic acids that are ubiquitous in the body and do not encode proteins, emerge as important regulatory factors in almost all biological processes in the brain. A wikibased, publicly editable and opencontent platform for community curation of human long noncoding rnas lncrnas lncbook. 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. The discovery of tens of thousands of ncrna species has revolutionized the field, altering the way that researchers think about physiology and the development of disease adams et al. We presented a method and developed a tool, lnctar, to predict the rna targets of long noncoding rnas. Functional annotation of structural ncrnas within enhancer rnas in the human genome. Multiple lines of evidence increasingly link mutations and dysregulations of lncrnas to diverse human diseases. Noncoding rnas in disease lekka 2018 febs letters wiley. For 50 years the term gene has been synonymous with regions of the genome encoding mrnas that are translated into protein. Long noncoding rnas expressed in human hepatic stellate.
Pdf circular rnas circrnas are a large class of noncoding rnas characterized with closed loop structures without 3. Human lncrnas participate in a spectrum of biological processes, for example, epigenetics, nuclear import, alternative splicing, rna decay and translation 2. Interest in the biological roles of long noncoding rnas lncrnas has resulted in growing numbers of studies that produce large sets of candidate genes, for example, differentially expressed between two conditions. 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. Here, we describe a comprehensive analysis of lncrna alterations at transcriptional, genomic, and epigenetic levels in 5,037 human tumor specimens across cancer types from the cancer genome atlas. Taft rj1, pang kc, mercer tr, dinger m, mattick js. Insights from global analyses of long noncoding rnas in.
Alterations in the primary structure, secondary structure, and expression levels of lncrnas as well as their cognate rnabinding proteins underlie diseases. Atoi rna editing is a posttranscriptional modification that converts adenosines to inosines in both coding and noncoding rna transcripts. Lnctar does not have limit to rna size, indicating lnctar can be used to all rnas. Noncoding rna is published quarterly online by mdpi. Basic science, human translational research studies and therapeutic development projects will be welcomed. Specifically in the mcf7 cell line, addition of 17. The human genome has been demonstrated to be pervasively transcribed, with a large fraction of the transcriptome representing non.
Regulatory transcripts can be either cisor transacting, and occur in intronic, intragenic and other untranslated regions of the genome. Long noncoding rnas and complex human diseases ncbi. Noncoding rnas are crucial in the development of several endocrine organs, as well as in endocrine diseases such as diabetes mellitus. Further, the book examines the function of lncrnas in diseases such as. The role of noncoding rnas in oncology sciencedirect. In parallel, a rapidly growing number of studies has unravelled associations between aberrant noncoding rna expression and human diseases. Author summary large intergenic noncoding rnas lincrnas are the largest class of noncoding rna molecules in the human genome. Long noncoding rnas lncrnas are emerging as important regulators of tissue physiology and disease processes including cancer. 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.
Human diseaseassociated genetic variation impacts large. Noncoding rnas, especially lncrnas, have emerged as key components in histone modification. Here, the authors perform a comprehensive rnai imaging screen targeting more than 2,000 human. About rnas, there is a clear evidence of the importance of noncoding rnas in central nervous system cns functions and their involvement in neurodegenerative diseases such as parkinsons. Frontiers comparison of noncoding rnas in human and. Extensive studies have suggested the involvement of noncoding rnas in brain development and neurodevelopmental disorders, and dysregulation of noncoding rnas is associated with abnormal. A new class of transcripts, long noncoding rnas lncrnas, has been recently found to be pervasively transcribed in the genome. Exosomal long noncoding rnas as biomarkers in human diseases. However, we are only beginning to understand the nature and extent of the involvement of noncoding rnas ncrnas in disease. The discovery of the posttranscriptional gene silencing ptgs by small nonproteincoding rnas is considered as a major breakthrough in biology. However, recent studies showed the proteincoding potential of ncrnas, indicating that they might be a source of some special proteins. Noncoding rnas is a cuttingedge topic in the scientific and medical fields, the identification of disease related ncrnas and their stateoftheart treatment approaches proceed at a fast pace. 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. Pdf circular rnas as novel biomarkers with regulatory.
The alterations in the epigenetic modifications of lncrnas underlie some human disorders ranging from. Here we summarize the latest promises and challenges of targeting noncoding rnas i n disease. Ptgs is a conserved phenomenon which was observed in various species such as fungi, worms, plants, and mammals. The complete understanding of the growing catalog of regulatory noncoding rnas is going to shed light in different aspects of a wide range of pathogenic mechanisms in human diseases. Special issue micrornas and other noncoding rnas in. They are likely caused by multiple genetic variants with low penetrance in combination with various environmental and lifestyle factors, and they do not simply obey the standard mendelian patterns of inheritance 59,60. Role of human noncoding rnas in the control of tumorigenesis. Errors of rna biology are common and found in association with both rare, single gene disorders, but also more common, chronic diseases. 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.
Adenosinetoinosine rna editing and human disease genome. 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. A highcontent rnai screen reveals multiple roles for long. Most noncoding rnas are considered by their expression at low levels and as having a limited phylogenetic distribution in the cytoplasm, indicating that they may be only involved in specific biological processes. Here, i focus on the genetic and epigenetic events that disrupt ncrna loci and their related proteins in the con text of cancer and other human diseases, such as neu. Comprehensive genomic characterization of long noncoding. 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.
Micrornas and long noncoding rnas in genetic diseases. Though not translated into proteins, ncrnas play pivotal roles in a variety of cellular functions. Complex diseases are multifactorial or polygenic disorders of the body. A library of human rna fragments was used to isolate, by affinity chromatography, 5 noncoding rna fragments that bind to human psf hpsf, releasing hpsf from a protooncogene and activating transcription. A rare disorder caused by loss of part of the long arm q arm, band 5q31. Long noncoding rnas lncrnas regulate key steps of cell division. Lnctar runs fast and therefore can be used for largescale identification of the rna targets for long noncoding rnas. 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 discovery of long noncoding rna lncrna has dramatically altered our understanding of cancer. In addition to examining micrornas, this volume provides a unique evaluation of more recently profiled noncoding rnas now implicated in carcinogenesis, including lncrnas, pirnas, circrnas, and trnas, identifying differences. Request pdf on apr 10, 2018, lei zhu and others published trnaderived small noncoding rnas in human disease find, read and cite all the research you need on researchgate. Special issue the role of noncoding rnas in human lung. A number of studies have revealed that lncrnas can participate in various critical biological processes, such as chromatin remodeling, gene. Although there are many challenges to be passed through, new forms and uses of.
Pdf the research progress of long noncoding rnas in. These transcripts are involved in many cellular processes, including the regulation of chromatin modification, gene transcription, mrna translation and protein function. Molecular functions and biological roles of long non. 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. 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. Cancer and noncoding rnas offers an indepth exploration of noncoding rnas and their role in epigenetic regulation of complex human disease, most notably cancer.
1542 470 499 90 504 227 1063 786 995 1268 1519 1620 68 909 337 1332 648 1408 766 856 375 1151 1553 1272 362 342 1190 1499 343 1498 620 948 1030 81 1060 638