non-coding transcription
Dotaz
Zobrazit nápovědu
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.
- Klíčová slova
- RNA polymerase II CTD, Sen1 helicase, non-coding transcription, pervasive transcription, transcription termination,
- MeSH
- DNA-helikasy chemie metabolismus MeSH
- fungální RNA metabolismus MeSH
- konformace proteinů MeSH
- molekulární modely MeSH
- nekódující RNA metabolismus MeSH
- proteinové domény MeSH
- proteiny vázající RNA chemie metabolismus MeSH
- regulace genové exprese u hub MeSH
- RNA-helikasy chemie metabolismus MeSH
- RNA-polymerasa II chemie MeSH
- Saccharomyces cerevisiae - proteiny chemie metabolismus MeSH
- Saccharomyces cerevisiae genetika metabolismus MeSH
- terminace genetické transkripce MeSH
- vazba proteinů MeSH
- vazebná místa MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA-helikasy MeSH
- fungální RNA MeSH
- nekódující RNA MeSH
- NRD1 protein, S cerevisiae MeSH Prohlížeč
- proteiny vázající RNA MeSH
- RNA-helikasy MeSH
- RNA-polymerasa II MeSH
- Saccharomyces cerevisiae - proteiny MeSH
- SEN1 protein, S cerevisiae MeSH Prohlížeč
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.
- Klíčová slova
- SR proteins, large intervening non-coding RNA, snRNP, spliceosomes, splicing,
- MeSH
- RNA dlouhá nekódující * genetika MeSH
- sestřih RNA MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- RNA dlouhá nekódující * 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
- lidé MeSH
- nádory genetika MeSH
- nekódující RNA genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- nekódující RNA MeSH
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 patients 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.
- Klíčová slova
- biosensing techniques, carcinogenesis, long non-coding RNA, tumor biomarkers,
- MeSH
- lidé MeSH
- nádorové biomarkery genetika MeSH
- nádory prostaty diagnóza genetika MeSH
- prognóza MeSH
- RNA dlouhá nekódující genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- nádorové biomarkery MeSH
- RNA dlouhá nekódující MeSH
Cytoplasmic male sterility (CMS) is a widespread phenomenon in flowering plants caused by mitochondrial (mt) genes. CMS genes typically encode novel proteins that interfere with mt functions and can be silenced by nuclear fertility-restorer genes. Although the molecular basis of CMS is well established in a number of crop systems, our understanding of it in natural populations is far more limited. To identify CMS genes in a gynodioecious plant, Silene vulgaris, we constructed mt transcriptomes and compared transcript levels and RNA editing patterns in floral bud tissue from female and hermaphrodite full siblings. The transcriptomes from female and hermaphrodite individuals were very similar overall with respect to variation in levels of transcript abundance across the genome, the extent of RNA editing, and the order in which RNA editing and intron splicing events occurred. We found only a single genomic region that was highly overexpressed and differentially edited in females relative to hermaphrodites. This region is not located near any other transcribed elements and lacks an open-reading frame (ORF) of even moderate size. To our knowledge, this transcript would represent the first non-coding mt RNA associated with CMS in plants and is, therefore, an important target for future functional validation studies.
- Klíčová slova
- Cytoplasmic male sterility, Silene vulgaris, editing, mitochondrion, non-coding RNA, splicing, transcriptome.,
- MeSH
- editace RNA MeSH
- květy genetika růst a vývoj MeSH
- mitochondriální geny * MeSH
- nekódující RNA * MeSH
- neplodnost rostlin * MeSH
- rostlinné proteiny genetika metabolismus MeSH
- Silene genetika fyziologie MeSH
- transkriptom * MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- Názvy látek
- nekódující RNA * MeSH
- rostlinné proteiny 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
- algoritmy MeSH
- bakteriální RNA chemie genetika MeSH
- druhová specificita MeSH
- genom bakteriální MeSH
- intergenová DNA MeSH
- konformace nukleové kyseliny MeSH
- molekulární modely MeSH
- nekódující RNA chemie genetika MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- Streptomyces coelicolor genetika MeSH
- Streptomyces genetika MeSH
- terminátorové oblasti (genetika) MeSH
- výpočetní biologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
- Názvy látek
- bakteriální RNA MeSH
- intergenová DNA MeSH
- nekódující RNA MeSH
OBJECTIVES: Long non-coding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides that are not translated into proteins. They are involved in pathogenesis of many diseases including cancer and have a potential to serve as diagnostic and prognostic markers. We aimed to investigate lncRNA expression profiles in bone marrow plasma cells (BMPCs) of newly diagnosed multiple myeloma (MM) patients in comparison to normal BMPCs of healthy donors (HD) in a three-phase biomarker study. METHODS: Expression profile of 83 lncRNA was performed by RT2 lncRNA PCR Array (Qiagen), followed by quantitative real-time PCR using specific TaqMan non-coding RNA assays analyzing 84 newly diagnosed MM patients and 25 HD. RESULTS: Our analysis revealed dysregulation of two lncRNAs; NEAT1 (sensitivity of 55.0% and specificity of 79.0%) and UCA1 (sensitivity of 85.0% and specificity of 94.7%). UCA1 levels correlated with albumin and monoclonal immunoglobulin serum levels, cytogenetic aberrations, and survival of MM patients. CONCLUSION: Our study suggests a possible prognostic impact of UCA1 expression levels on MM patients.
- Klíčová slova
- biomarker, long non-coding RNA, multiple myeloma, plasma cells, prognosis, quantitative real-time PCR,
- MeSH
- biologické markery MeSH
- chromozomální aberace MeSH
- diferenciální diagnóza MeSH
- hybridizace in situ fluorescenční MeSH
- Kaplanův-Meierův odhad MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- mnohočetný myelom diagnóza genetika mortalita terapie MeSH
- nádorové biomarkery * MeSH
- prognóza MeSH
- regulace genové exprese u nádorů * MeSH
- RNA dlouhá nekódující genetika MeSH
- ROC křivka MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- stanovení celkové genové exprese MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- nádorové biomarkery * MeSH
- NEAT1 long non-coding RNA, human MeSH Prohlížeč
- RNA dlouhá nekódující MeSH
- UCA1 RNA, human MeSH Prohlížeč
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.
- Klíčová slova
- Cancer, LINC00467, Oncogene, lncRNA, miRNA,
- MeSH
- beta-katenin genetika MeSH
- biologické markery MeSH
- karcinogeneze genetika MeSH
- lidé MeSH
- mikro RNA * genetika MeSH
- nádorové buněčné linie MeSH
- nádory * genetika MeSH
- NF-kappa B MeSH
- onkogeny genetika MeSH
- proliferace buněk genetika MeSH
- protoonkogenní proteiny c-akt genetika MeSH
- regulace genové exprese u nádorů MeSH
- RNA dlouhá nekódující * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- beta-katenin MeSH
- biologické markery MeSH
- mikro RNA * MeSH
- NF-kappa B MeSH
- protoonkogenní proteiny c-akt MeSH
- RNA dlouhá nekódující * MeSH
Long non-coding RNAs (lncRNAs) are a highly heterogeneous class of non-protein-encoding transcripts that play an essential regulatory role in diverse biological processes, including stress responses. The severe stunting disease caused by Citrus bark cracking viroid (CBCVd) poses a major threat to the production of Humulus lupulus (hop) plants. In this study, we systematically investigate the characteristics of the lncRNAs in hop and their role in CBCVd-infection using RNA-sequencing data. Following a stringent filtration criterion, a total of 3598 putative lncRNAs were identified with a high degree of certainty, of which 19% (684) of the lncRNAs were significantly differentially expressed (DE) in CBCVd-infected hop, which were predicted to be mainly involved in plant-pathogen interactions, kinase cascades, secondary metabolism and phytohormone signal transduction. Besides, several lncRNAs and CBCVd-responsive lncRNAs were identified as the precursor of microRNAs and predicted as endogenous target mimics (eTMs) for hop microRNAs involved in CBCVd-infection.
- Klíčová slova
- Citrus bark cracking viroid, Genomics, Humulus lupulus, Long non-coding RNAs, Plant defense, RNA-sequencing,
- MeSH
- Citrus * genetika MeSH
- Humulus * genetika MeSH
- kůra rostlin MeSH
- nemoci rostlin genetika MeSH
- RNA dlouhá nekódující * genetika MeSH
- stanovení celkové genové exprese MeSH
- viroidy * genetika MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- RNA dlouhá nekódující * MeSH
Whole-genome sequencing analyses revealed that the majority of the human genome is transcribed and identified thousands of protein non-coding transcripts. Non-coding RNAs (ncRNAs) are divided into two main groups: small and long ncRNAs. This review is focused on the regulatory ncRNAs mainly on microRNAs and long ncRNAs. These ncRNAs regulate gene expression at the transcriptional and post-transcriptional levels. In this context, ncRNAs are involved in the regulation of most cellular processes and their deregulation has serious impacts on the phenotype. Hundreds of studies have implicated ncRNAs in the pathogenesis of many diseases ranging from metabolic disorders to diseases of organ systems as well as various types of cancers.Clinically, ncRNAs belong to a new generation of diagnostic and prognostic biomarkers with a great potential. Due to high tissue specificity and ability to regulate multiple genes often within one signaling pathway, ncRNAs represent attractive therapeutic targets. Increasing knowledge about a wide spectrum of ncRNA actions demonstrate a pivotal role of these transcripts in expression regulation. Many aspects of the ncRNA biology are still unclear and their understanding will provide us a new perspective on the complexity of the regulatory network.
- Klíčová slova
- gene expression regulation, miRNA lncRNA., non-coding RNA,
- MeSH
- lidé MeSH
- mikro RNA genetika fyziologie MeSH
- nekódující RNA genetika fyziologie MeSH
- regulace genové exprese genetika fyziologie MeSH
- RNA dlouhá nekódující genetika fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- mikro RNA MeSH
- nekódující RNA MeSH
- RNA dlouhá nekódující MeSH