Although the existence of small molecules of RNA that do not encode any amino acid chain has been proven two decades ago, their significance and extensive effect on cellular processes is still amazing. Many new studies fo-cused on finding new non-coding RNAs and the clarifica-tion of their functions in the organism are continuously published. This paper summarizes the current knowledge of small non-coding RNAs and their functions, both in prokaryotic and eukaryotic organisms.
Content -- INTRODUCTION .З -- CHAPTER I: Non-coding RNAs 5 -- 1.1 Small non-coding RNAs .6 -- 1.1.1 MicroRNAs 6 -- 1.1.2 Small interfering RNAs .7 -- 1.1.3 PIWI proteins associated RNAs 8 -- 1.1.4 Small nucleolar RNAs .9 -- 1.2 Long non-coding RNAs .10 -- 1.2.1 Long intergenic non-coding RNAs .11 -- 1.2.2 Transcribed-ultraconserved regions 11 -- CHAPTER II: Expression Profiling of Non-coding RNAs 15 -- 2.1 Oesophageal cancer .15 - 55 -- 5.4 Gallbladder cancer .56 -- 5.5 Colorectal cancer 56 -- CHAPTER VI: Non-coding RNAs as Potential
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- MeSH
- Gastrointestinal Neoplasms diagnosis MeSH
- Biomarkers, Tumor MeSH
- RNA, Untranslated MeSH
- Gene Expression Profiling MeSH
- Conspectus
- Patologie. Klinická medicína
- NML Fields
- gastroenterologie
- biologie
- NML Publication type
- studie
Lidský genom obsahuje asi 22 000 protein kódujících genů, které dávají vznik ještě většímu množství messengerové RNA (mRNA). Výsledky projektu ENCODE z roku 2012 však ukazují, že byť je až 90 % našeho genomu aktivně přepisováno, tak mRNA dávající vznik proteinům tvoří pouze 2–3 % z celkového množství přepsané RNA. Zbývající RNA transkripty nedávají vznik proteinům a nesou proto označení „nekódující RNA“. Dříve se nekódující RNA považovala za „temnou hmotu genomu“, nebo za „odpad“, který se v naší DNA nahromadil v průběhu evoluce. Dnes již víme, že nekódující RNA plní v našem těle celou řadu regulačních funkcí – zasahují do epigenetických procesů od remodelace chromatinu k metylaci histonů, nebo do vlastního procesu transkripce, či do posttranskripčních procesů. Dlouhé nekódující RNA (lncRNA) jsou jednou ze tříd nekódujících RNA s délkou nad 200 nukleotidů (nekódující RNA s délkou pod 200 nukleotidů označujeme jako krátké nekódující RNA). lncRNA představují velice pestrou a rozsáhlou skupinu molekul s rozličnými regulačními funkcemi. Můžeme je identifkovat ve všech myslitelných buněčných typech, či tkáních, nebo dokonce v extracelulárním prostoru, a to včetně krve, potažmo plazmy. Jejich hladiny se mění v průběhu organogeneze, jsou specifické pro jednotlivé tkáně a k jejich změnám dochází i při vzniku různých onemocnění, včetně aterosklerózy. Cílem tohoto souhrnného článku je jednak představit problematiku lncRNA a některé jejich konkrétní zástupce ve vztahu k procesu aterosklerózy (popsat zapojení lncRNA do biologie endotelových buněk, hladkosvalových buněk cévní stěny, či buněk imunitních), a dále poukázat na možný klinický potenciál lncRNA, ať již v diagnostice či terapii aterosklerózy a jejích klinických manifestací.
The human genome contains about 22 000 protein-coding genes that are transcribed to an even larger amount of messenger RNAs (mRNA). Interestingly, the results of the project ENCODE from 2012 show, that despite up to 90 % of our genome being actively transcribed, protein-coding mRNAs make up only 2–3 % of the total amount of the transcribed RNA. The rest of RNA transcripts is not translated to proteins and that is why they are referred to as “non-coding RNAs”. Earlier the non-coding RNA was considered “the dark matter of genome”, or “the junk”, whose genes has accumulated in our DNA during the course of evolution. Today we already know that non-coding RNAs fulfil a variety of regulatory functions in our body – they intervene into epigenetic processes from chromatin remodelling to histone methylation, or into the transcription process itself, or even post-transcription processes. Long non-coding RNAs (lncRNA) are one of the classes of non-coding RNAs that have more than 200 nucleotides in length (non-coding RNAs with less than 200 nucleotides in length are called small non-coding RNAs). lncRNAs represent a widely varied and large group of molecules with diverse regulatory functions. We can identify them in all thinkable cell types or tissues, or even in an extracellular space, which includes blood, specifically plasma. Their levels change during the course of organogenesis, they are specific to different tissues and their changes also occur along with the development of different illnesses, including atherosclerosis. This review article aims to present lncRNAs problematics in general and then focuses on some of their specific representatives in relation to the process of atherosclerosis (i.e. we describe lncRNA involvement in the biology of endothelial cells, vascular smooth muscle cells or immune cells), and we further describe possible clinical potential of lncRNA, whether in diagnostics or therapy of atherosclerosis and its clinical manifestations.
- MeSH
- Atherosclerosis * physiopathology MeSH
- Endothelium physiology MeSH
- Gene Expression MeSH
- Humans MeSH
- RNA, Long Noncoding * physiology classification MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Osteoarthritis (OA) is a frequent musculoskeletal disorder affecting millions of people worldwide. Despite advances in understanding the pathogenesis of OA, prognostic biomarkers or effective targeted treatment are not currently available. Research on epigenetic factors has yielded some new insights as new technologies for their detection continue to emerge. In this context, non-coding RNAs, including microRNAs, long non-coding RNAs, circular RNAs, piwi-interacting RNAs, and small nucleolar RNAs, regulate intracellular signaling pathways and biological processes that have a crucial role in the development of several diseases. In this review, we present current knowledge on the role of epigenetic factors with a focus on non-coding RNAs in the development, prediction and treatment of OA. This article is categorized under: RNA in Disease and Development > RNA in Disease.
- MeSH
- RNA, Circular MeSH
- Humans MeSH
- MicroRNAs * genetics MeSH
- Osteoarthritis * genetics MeSH
- Piwi-Interacting RNA MeSH
- RNA, Long Noncoding * genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Většinu eukaryotického genomu představují DNA sekvence, které nekódují proteiny. Tyto sekvence jsou přepisovány buď podle vývojového programu daného organizmu nebo v rámci odpovědi na vnější signály. Výsledkem transkripce takových sekvencí je pak velké množství dlouhých nekódujících RNA (lncRNA). Celogenomové studie předpokládají existenci více než 3 300 lncRNA. Dlouhé nekódující RNA jsou definovány jako molekuly nekódujících RNA o délce více než 200 nukleotidů. Vzhledem k vysoké míře komplexnosti a rozmanitosti těchto sekvencí byl nárůst poznání v této oblasti relativně pomalý. Ačkoli bylo dosud funkčně charakterizováno pouze omezené množství lncRNA, jejich regulační potenciál je již dnes evidentní. LncRNA hrají klíčové role jak v transkripčních, tak v post-transkripčních regulačních drahách. U mnoha nádorových onemocnění dochází k deregulaci lncRNA, což společně s jejich funkčními vlastnostmi naznačuje jejich významný potenciál v procesech maligní transformace. Tento přehledový článek je zaměřen na shrnutí nedávno objevených skupin lncRNA, popis jejich biologických funkcí a zejména na jejich význam v nádorové biologii a translačním onkologickém výzkumu.
A major portion of the eukaryotic genome is occupied by DNA sequences; transcripts of these sequences do not code for proteins. This part of the eukaryotic genome is transcribed in a developmentally regulated manner or as a response to external stimuli to produce large numbers of long non-coding RNAs (lncRNAs). Genome-wide studies indicate the existence of more than 3,300 lncRNAs. Long non-coding RNAs are tentatively defined as molecules of ncRNAs that are more than two hundred nucleotides long. Due to the complexity and diversity of their sequences, progress in the field of lncRNAs has been very slow. Nonetheless, lncRNAs have emerged as key molecules involved in the control of transcriptional and posttranscriptional gene regulatory pathways. Although limited numbers of functional lncRNAs have been identified so far, the immense regulatory potential of lncRNAs is already evident, emphasizing that a genome-wide characterization of functional lncRNAs is needed. The fact that many lncRNAs are deregulated in various human cancers, together with their functional characteristics, implies their eminent role in carcinogenesis. In this review, we summarize novel classes of lncRNAs, describe their biological functions emphasizing their roles in tumor biology and translational oncology research.
- Keywords
- lincRNA, T-UC,
- MeSH
- 3' Untranslated Regions physiology genetics immunology MeSH
- 5' Untranslated Regions physiology genetics immunology MeSH
- Financing, Organized MeSH
- Genetic Markers genetics MeSH
- Genetic Structures MeSH
- Genome, Human physiology genetics immunology MeSH
- Carcinoma, Hepatocellular diagnosis genetics MeSH
- Humans MeSH
- RNA, Small Untranslated genetics isolation & purification MeSH
- MicroRNAs genetics isolation & purification MeSH
- Prostatic Neoplasms diagnosis genetics MeSH
- Breast Neoplasms diagnosis genetics MeSH
- Neoplasms diagnosis etiology genetics MeSH
- RNA, Untranslated diagnostic use genetics isolation & purification MeSH
- Untranslated Regions physiology genetics immunology MeSH
- Telomere-Binding Proteins genetics MeSH
- Pseudogenes physiology genetics immunology MeSH
- Translational Research, Biomedical methods trends MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
BACKGROUND: The first systematic study of small non-coding RNAs (sRNA, ncRNA) in Streptomyces is presented. Except for a few exceptions, the Streptomyces sRNAs, as well as the sRNAs in other genera of the Actinomyces group, have remained unstudied. This study was based on sequence conservation in intergenic regions of Streptomyces, localization of transcription termination factors, and genomic arrangement of genes flanking the predicted sRNAs. RESULTS: Thirty-two potential sRNAs in Streptomyces were predicted. Of these, expression of 20 was detected by microarrays and RT-PCR. The prediction was validated by a structure based computational approach. Two predicted sRNAs were found to be terminated by transcription termination factors different from the Rho-independent terminators. One predicted sRNA was identified computationally with high probability as a Streptomyces 6S RNA. Out of the 32 predicted sRNAs, 24 were found to be structurally dissimilar from known sRNAs. CONCLUSION: Streptomyces is the largest genus of Actinomyces, whose sRNAs have not been studied. The Actinomyces is a group of bacterial species with unique genomes and phenotypes. Therefore, in Actinomyces, new unique bacterial sRNAs may be identified. The sequence and structural dissimilarity of the predicted Streptomyces sRNAs demonstrated by this study serve as the first evidence of the uniqueness of Actinomyces sRNAs.
- MeSH
- Algorithms MeSH
- RNA, Bacterial genetics chemistry MeSH
- Species Specificity MeSH
- Financing, Organized MeSH
- Genome, Bacterial MeSH
- DNA, Intergenic MeSH
- Nucleic Acid Conformation MeSH
- Models, Molecular MeSH
- RNA, Untranslated genetics chemistry MeSH
- Reverse Transcriptase Polymerase Chain Reaction MeSH
- Base Sequence MeSH
- Oligonucleotide Array Sequence Analysis MeSH
- Streptomyces coelicolor genetics MeSH
- Streptomyces genetics MeSH
- Terminator Regions, Genetic MeSH
- Computational Biology MeSH
Cardiac arrhythmias represent wide and heterogenic group of disturbances in the cardiac rhythm. Pathophysiology of individual arrhythmias is highly complex and dysfunction in ion channels/currents involved in generation or spreading of action potential is usually documented. Non-coding RNAs (ncRNAs) represent highly variable group of molecules regulating the heart expression program, including regulation of the expression of individual ion channels and intercellular connection proteins, e.g. connexins.Within this chapter, we will describe basic electrophysiological properties of the myocardium. We will focus on action potential generation and spreading in pacemaker and non-pacemaker cells, including description of individual ion channels (natrium, potassium and calcium) and their ncRNA-mediated regulation. Most of the studies have so far focused on microRNAs, thus, their regulatory function will be described into greater detail. Clinical consequences of altered ncRNA regulatory function will also be described together with potential future directions of the research in the field.
- MeSH
- Ion Channels MeSH
- Humans MeSH
- MicroRNAs MeSH
- RNA, Untranslated * MeSH
- Heart MeSH
- Arrhythmias, Cardiac * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
The majority of the human genome encodes RNAs that do not code for proteins. These non-coding RNAs (ncRNAs) affect normal expression of the genes, including oncogenes and tumour suppressive genes, which make them a new class of targets for drug development in cancer. Although microRNAs (miRNAs) are the most studied regulatory ncRNAs to date, and miRNA-targeted therapeutics have already reached clinical development, including the mimics of the tumour suppressive miRNAs miR-34 and miR-16, which reached phase I clinical trials for the treatment of liver cancer and mesothelioma, the importance of long non-coding RNAs (lncRNAs) is increasingly being recognised. Here, we describe obstacles and advances in the development of ncRNA therapeutics and provide the comprehensive overview of the ncRNA chemistry and delivery technologies. Furthermore, we summarise recent knowledge on the biological functions of miRNAs and their involvement in carcinogenesis, and discuss the strategies of their therapeutic manipulation in cancer. We review also the emerging insights into the role of lncRNAs and their potential as targets for novel treatment paradigms. Finally, we provide the up-to-date summary of clinical trials involving miRNAs and future directions in the development of ncRNA therapeutics.
- MeSH
- Molecular Targeted Therapy methods trends MeSH
- Humans MeSH
- MicroRNAs genetics MeSH
- Models, Genetic MeSH
- Neoplasms drug therapy genetics MeSH
- RNA, Untranslated genetics MeSH
- Antineoplastic Agents therapeutic use MeSH
- Gene Expression Regulation, Neoplastic drug effects MeSH
- RNA, Long Noncoding genetics MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Cells must change their properties in order to adapt to a constantly changing environment. Most of the cellular sensing and regulatory mechanisms described so far are based on proteins that serve as sensors, signal transducers, and effectors of signalling pathways, resulting in altered cell physiology. In recent years, however, remarkable examples of the critical role of non-coding RNAs in some of these regulatory pathways have been described in various organisms. In this review, we focus on all classes of non-coding RNAs that play regulatory roles during stress response, starvation, and ageing in different yeast species as well as in structured yeast populations. Such regulation can occur, for example, by modulating the amount and functional state of tRNAs, rRNAs, or snRNAs that are directly involved in the processes of translation and splicing. In addition, long non-coding RNAs and microRNA-like molecules are bona fide regulators of the expression of their target genes. Non-coding RNAs thus represent an additional level of cellular regulation that is gradually being uncovered.
- MeSH
- MicroRNAs * genetics MeSH
- RNA, Long Noncoding * genetics MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
For the many years, the central dogma of molecular biology has been that RNA functions mainly as an informational intermediate between a DNA sequence and its encoded protein. But one of the great surprises of modern biology was the discovery that protein-coding genes represent less than 2% of the total genome sequence, and subsequently the fact that at least 90% of the human genome is actively transcribed. Thus, the human transcriptome was found to be more complex than a collection of protein-coding genes and their splice variants. Although initially argued to be spurious transcriptional noise or accumulated evolutionary debris arising from the early assembly of genes and/or the insertion of mobile genetic elements, recent evidence suggests that the non-coding RNAs (ncRNAs) may play major biological roles in cellular development, physiology and pathologies. NcRNAs could be grouped into two major classes based on the transcript size; small ncRNAs and long ncRNAs. Each of these classes can be further divided, whereas novel subclasses are still being discovered and characterized. Although, in the last years, small ncRNAs called microRNAs were studied most frequently with more than ten thousand hits at PubMed database, recently, evidence has begun to accumulate describing the molecular mechanisms by which a wide range of novel RNA species function, providing insight into their functional roles in cellular biology and in human disease. In this review, we summarize newly discovered classes of ncRNAs, and highlight their functioning in cancer biology and potential usage as biomarkers or therapeutic targets.