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

In this review I focus on the role of splicing in long non-coding RNA (lncRNA) life. First, I summarize differences between the splicing efficiency of protein-coding genes and lncRNAs and discuss why non-coding RNAs are spliced less efficiently. In the second half of the review, I speculate why splice sites are the most conserved sequences in lncRNAs and what additional roles could splicing play in lncRNA metabolism. I discuss the hypothesis that the splicing machinery can, besides its dominant role in intron removal and exon joining, protect cells from undesired transcripts.

• MeSH
• RNA, Long Noncoding * genetics   MeSH
• RNA Splicing MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Pervasive transcription is a widespread phenomenon leading to the production of a plethora of non-coding RNAs (ncRNAs) without apparent function. Pervasive transcription poses a threat to proper gene expression that needs to be controlled. In yeast, the highly conserved helicase Sen1 restricts pervasive transcription by inducing termination of non-coding transcription. However, the mechanisms underlying the specific function of Sen1 at ncRNAs are poorly understood. Here, we identify a motif in an intrinsically disordered region of Sen1 that mimics the phosphorylated carboxy-terminal domain (CTD) of RNA polymerase II, and structurally characterize its recognition by the CTD-interacting domain of Nrd1, an RNA-binding protein that binds specific sequences in ncRNAs. In addition, we show that Sen1-dependent termination strictly requires CTD recognition by the N-terminal domain of Sen1. We provide evidence that the Sen1-CTD interaction does not promote initial Sen1 recruitment, but rather enhances Sen1 capacity to induce the release of paused RNAPII from the DNA. Our results shed light on the network of protein-protein interactions that control termination of non-coding transcription by Sen1.

• MeSH
• DNA Helicases chemistry   metabolism   MeSH
• RNA, Fungal metabolism   MeSH
• Protein Conformation MeSH
• Models, Molecular MeSH
• RNA, Untranslated metabolism   MeSH
• Protein Domains MeSH
• RNA-Binding Proteins chemistry   metabolism   MeSH
• Gene Expression Regulation, Fungal MeSH
• RNA Helicases chemistry   metabolism   MeSH
• RNA Polymerase II chemistry   MeSH
• Saccharomyces cerevisiae Proteins chemistry   metabolism   MeSH
• Saccharomyces cerevisiae genetics   metabolism   MeSH
• Transcription Termination, Genetic MeSH
• Protein Binding MeSH
• Binding Sites MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Dlouhé nekódující molekuly RNA (long non-coding RNA – lncRNA) jsou definovány jako molekuly o délce více než 200 nukleotidů, které jsou lokalizovány v jádře a cytoplazmě buněk. Přestože u většiny lncRNA jejich konkrétní funkce nejsou dosud známé, je evidentní, že se podílejí na celé řadě biologických procesů. LncRNA hrají klíčové role jak v transkripčních, tak v post‐transkripčních regulačních drahách a podílejí se na významných buněčných procesech, jako je proliferace, diferenciace, apoptóza a v neposlední řadě i na patogenezi různých nemocí. Svou deregulací se významně podílejí také na procesech nádorové transformace. V tomto přehledovém článku jsou popsány vlastnosti, funkce a molekulární podstata lncRNA a také jejich diagnostický potenciál. Pozornost je věnována zejména jejich využití u nejčastěji diagnostikovaných nádorových onemocnění v české populaci, a to u kolorektálního karcinomu, karcinomu prsu a prostaty.

Long non-coding RNA molecules (lncRNA) are defined as molecules over 200 nucleotides long that are localized in the nucleus and cytoplasm of cells. Although function of most lnRNA is not known, it is obvious that they are involved in various biological processes. LncRNA play a key role in transcriptional as well as post‐transcriptional regulatory pathways and are involved in important cell processes, such as proliferation, differentiation, apoptosis but also pathogenesis of various diseases. Their dysregulation is important in steps of tumor transformation. In this review, we will describe the nature, function and molecular basis of these molecules as well as their diagnostic potential. The main focus of this review is the usage of these molecules in the most often diagnosed tumors in the Czech population – colorectal carcinoma, breast and prostate carcinomas. Key words: long non-coding RNA molecules – tumor markers – lncRNA deregulation – solid tumors This work was supported by the grant of the Czech Ministry of Health AZV 15-29508A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 23. 10. 2015 Accepted: 2. 12. 2015

• MeSH
• Colorectal Neoplasms genetics   MeSH
• Humans MeSH
• Biomarkers, Tumor MeSH
• Prostatic Neoplasms genetics   MeSH
• Breast Neoplasms genetics   MeSH
• Gene Expression Regulation, Neoplastic * MeSH
• RNA, Long Noncoding * analysis   isolation & purification   classification   MeSH
• Signal Transduction genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Východiska: Dlouhé nekódující RNA (long non-coding RNA – lncRNA) jsou RNA molekuly o délce větší než 200 nukleotidů, které ovlivňují řadu fyziologických funkcí a mají významnou regulační roli v buňkách. Jejich hladiny jsou často změněny u různých malignit, a představují tak slibný biomarker pro diagnostiku, prognózu nebo rekurenci nádorových onemocnění. Díky důležitosti těchto molekul výrazně roste i počet publikací na toto téma. Mezi nejčastěji studované lncRNA patří např. HOTAIR, MALAT1 a PCA3. Cíl: V současné době jsou vyvíjeny různé metody pro analýzu či detekci lncRNA, obvykle založené na optických metodách pro detekci mediátorové RNA (mRNA), např. polymerázová řetězová reakce s reverzní transkripcí, fl uorescenční in situ hybridizace nebo sekvenování nové generace. Je však potřeba dbát na rozdíly ve struktuře mRNA a lncRNA. V této práci popisujeme nejenom standardní metody, ale i nové přístupy pro detekci lncRNA zahrnující např. chemiluminescenční a elektrochemické techniky. Závěr: I navzdory pokrokům a velkému množství publikovaných prací existuje pouze jeden schválený diagnostický test založený na detekci lncRNA, a to PCA3 test pro diagnostiku karcinomu prostaty analýzou moči. Ostatní jsou v současnosti pouze ve fázi vývoje a bude potřeba je validovat. Dia gnostika založená na lncRNA i tak skýtá obrovský potenciál, a je proto velmi pravděpodobné, že se v blízké době objeví další diagnostické testy cílící na jiné typy lncRNA.

Background: Long non-coding RNAs (lncRNA) are more than 200-nucleotide-long RNA molecules that affect multiple physiologic phenomena and have important regulatory functions in cells. Their levels are often altered in various malignancies, thus they represent a potential biomarker for the diagnostics, prognosis or recurrence of cancer. Their importance has recently led to an enormous increase in a number of publications on the subject. The most frequently studied lncRNAs are HOTAIR, MALAT1 and PCA3. Aim: Numerous methods are currently being developed for the analysis or detection of lncRNA. They are mostly based on optical methods used for the detection of messenger RNAs, including polymerase chain reaction with reverse transcription, fluorescence in situ hybridisation or next-generation sequencing, but caution must be taken due to their structural differences. Here, we describe not only standard but also novel techniques for lncRNA detection, including chemiluminescent and electrochemical techniques. Conclusion: Despite the great progress and plethora of papers on this topic, there is only one single approved lncRNA-based diagnostic test, a PCA3 test for the diagnosis of prostate cancer from the patient’s urine. All other tests are only in their research phase and need to be validated. Nevertheless, lncRNA diagnostics offer enormous potential and thus it is highly probable that other diagnostic tests on different lncRNA types will soon appear.

• MeSH
• Biosensing Techniques methods   MeSH
• Carcinogenesis MeSH
• Humans MeSH
• Biomarkers, Tumor * MeSH
• RNA, Long Noncoding * analysis   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't 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.

• MeSH
• Humans MeSH
• Neoplasms genetics   MeSH
• RNA, Untranslated genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

Východiska: Rakovina děložního čípku jako běžný urogenitální nádor způsobuje u žen značné zdravotní problémy. Byla vynaložena snaha o identifikaci patogeneze za účelem nalezení cílených terapií. Bylo prokázáno, že dlouhé nekódující ribonukleové kyseliny (lncRNA) regulují několik signálních drah a genů souvisejících s nádory, což přispívá k patogenezi lidských malignit vč. rakoviny děložního čípku. V rámci prezentovaného článku jsme do prosince 2017 vyhledávali klíčová slova "cervical cancer" (rakovina děložního čípku) nebo "cervical neoplasm" (cervikální novotvar) a "long non-coding RNA" (dlouhá nekódující RNA) nebo "lncRNA", publikovaná v databázi PubMed, Google scholar, Web of Science a Scopus. Cíl: Zjistit, jakou roli hrají lncRNA v rakovině děložního čípku. Závěry: LncRNA ovlivňují patogenezi rakoviny děložního čípku prostřednictvím četných mechanismů, jako je vytváření tzv. scaffolds pro sestavení proteinových komplexů, sloužící jako tzv. directors pro získávání proteinů, fungujících jako transkripční zesilovače pomocí remodelování chromatinu, sloužící jako tzv. návnady k uvolnění proteinů z chromatinu nebo zvrácení účinků jiné regulační nekódující RNA jako jsou mikroRNA. Analýza signálních drah ukázala, že v procesu patogeneze rakoviny děložního čípku několik lncRNA reguluje dráhy PI3K/ Akt/ mTOR, Wnt-β catenin a Notch signální dráhy. Navíc exprese několika lncRNA byla spojena s infekcí virem lidského papilomu. Identifikace lncRNA, které mění signální dráhy související s nádory, a následná expresní analýza těchto lncRNA ve vzorcích pacientů by mohly pomoci získat efektivní cílené terapie.

Summary Background: Cervical cancer as a common urogenital cancer among women has caused signifi - cant health problems. Efforts have been made to identify its pathogenic process in order to find targeted ther apies. Long non-cod ing ribonucleic acids (lncRNAs) have been shown to regulate several cancer-related pathways and genes that contribute to pathogenesis of human malignancies, includ ing cervical cancer. In the present review, we searched PubMed, Google scholar, Web of Science and Scopus databases for key words "cervical cancer" or "cervical neoplasm" and "long non-coding RNA" or "lncRNA" (up to December 2017). Aim: To elaborate the role of lncRNAs in cervical cancer. Conclusions: LncRNAs affect cervical cancer pathogenesis through numerous mechanisms, such as making scaffolds for assembly of protein complexes, serving as directors to recruit proteins, functioning as transcriptional enhancers through chromatin remodeling, serving as decoys to free up proteins from chromatin, or revers ing the effects of other regulatory non-cod ing RNAs, such as microRNAs. Pathway-based analysis showed that several lncRNAs modulate PI3K/ Akt/ mTOR, Wnt-β catenin and Notch pathways in the process of cervical cancer pathogenesis. In addition, expression of a handful of lncRNAs has been associated with human papilloma virus infection. Identification of lncRNAs that alter cancer-related signaling pathways and subsequent expression analysis of these lncRNAs in patients’ samples would help to design ef ective targeted ther apies.

• MeSH
• Humans MeSH
• Uterine Cervical Neoplasms * genetics   MeSH
• Oncogenes MeSH
• RNA, Long Noncoding * MeSH
• Genes, Tumor Suppressor MeSH
• Check Tag
• Humans MeSH
• Female 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

The significance of long non-coding RNAs (lncRNAs) in the development and progression of human cancers has attracted increasing attention in recent years of investigations. Having versatile interactions and diverse functions, lncRNAs can act as oncogenes or tumor-suppressors to actively regulate cell proliferation, survival, stemness, drug resistance, invasion and metastasis. LINC00467, an oncogenic member of long intergenic non-coding RNAs, is upregulated in numerous malignancies and its high expression is often related to poor clinicopathological features. LINC00467 facilitates the progression of cancer via sponging tumor-suppressive microRNAs, inhibiting cell death cascade, modulating cell cycle controllers, and regulating signalling pathways including AKT, STAT3, NF-κB and Wnt/β-catenin. A growing number of studies have revealed that LINC00467 may serve as a novel prognostic biomarker and its inhibitory targeting has a valuable therapeutic potential to suppress the malignant phenotypes of cancer cells. In the present review, we discuss the importance of LINC00467 and provide a comprehensive collection of its functions and molecular mechanisms in a variety of cancer types.

• MeSH
• beta Catenin genetics   MeSH
• Biomarkers MeSH
• Carcinogenesis genetics   MeSH
• Humans MeSH
• MicroRNAs * genetics   MeSH
• Cell Line, Tumor MeSH
• Neoplasms * genetics   MeSH
• NF-kappa B MeSH
• Oncogenes genetics   MeSH
• Cell Proliferation genetics   MeSH
• Proto-Oncogene Proteins c-akt genetics   MeSH
• Gene Expression Regulation, Neoplastic MeSH
• RNA, Long Noncoding * genetics   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

• 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