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.

• Keywords
• RNA polymerase II CTD, Sen1 helicase, non-coding transcription, pervasive transcription, transcription termination,
• 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
• Names of Substances
• DNA Helicases MeSH
• RNA, Fungal MeSH
• RNA, Untranslated MeSH
• NRD1 protein, S cerevisiae MeSH Browser
• RNA-Binding Proteins MeSH
• RNA Helicases MeSH
• RNA Polymerase II MeSH
• Saccharomyces cerevisiae Proteins MeSH
• SEN1 protein, S cerevisiae MeSH Browser

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.

• Keywords
• SR proteins, large intervening non-coding RNA, snRNP, spliceosomes, splicing,
• MeSH
• RNA, Long Noncoding * genetics   MeSH
• RNA Splicing MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• RNA, Long Noncoding * 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
• Names of Substances
• RNA, Untranslated 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.

• Keywords
• biosensing techniques, carcinogenesis, long non-coding RNA, tumor biomarkers,
• MeSH
• Humans MeSH
• Biomarkers, Tumor genetics   MeSH
• Prostatic Neoplasms diagnosis   genetics   MeSH
• Prognosis MeSH
• RNA, Long Noncoding genetics   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Biomarkers, Tumor MeSH
• RNA, Long Noncoding 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.

• Keywords
• Cytoplasmic male sterility, Silene vulgaris, editing, mitochondrion, non-coding RNA, splicing, transcriptome.,
• MeSH
• RNA Editing MeSH
• Flowers genetics   growth & development   MeSH
• Genes, Mitochondrial * MeSH
• RNA, Untranslated * MeSH
• Plant Infertility * MeSH
• Plant Proteins genetics   metabolism   MeSH
• Silene genetics   physiology   MeSH
• Transcriptome * MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Names of Substances
• RNA, Untranslated * MeSH
• Plant Proteins 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 chemistry   genetics   MeSH
• Species Specificity MeSH
• Genome, Bacterial MeSH
• DNA, Intergenic MeSH
• Nucleic Acid Conformation MeSH
• Models, Molecular MeSH
• RNA, Untranslated chemistry   genetics   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
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Validation Study MeSH
• Names of Substances
• RNA, Bacterial MeSH
• DNA, Intergenic MeSH
• RNA, Untranslated 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.

• Keywords
• biomarker, long non-coding RNA, multiple myeloma, plasma cells, prognosis, quantitative real-time PCR,
• MeSH
• Biomarkers MeSH
• Chromosome Aberrations MeSH
• Diagnosis, Differential MeSH
• In Situ Hybridization, Fluorescence MeSH
• Kaplan-Meier Estimate MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Middle Aged MeSH
• Humans MeSH
• Multiple Myeloma diagnosis   genetics   mortality   therapy   MeSH
• Biomarkers, Tumor * MeSH
• Prognosis MeSH
• Gene Expression Regulation, Neoplastic * MeSH
• RNA, Long Noncoding genetics   MeSH
• ROC Curve MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Neoplasm Staging MeSH
• Gene Expression Profiling MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers MeSH
• Biomarkers, Tumor * MeSH
• NEAT1 long non-coding RNA, human MeSH Browser
• RNA, Long Noncoding MeSH
• UCA1 RNA, human MeSH Browser

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.

• Keywords
• Cancer, LINC00467, Oncogene, lncRNA, miRNA,
• 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
• Names of Substances
• beta Catenin MeSH
• Biomarkers MeSH
• MicroRNAs * MeSH
• NF-kappa B MeSH
• Proto-Oncogene Proteins c-akt MeSH
• RNA, Long Noncoding * 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.

• Keywords
• Citrus bark cracking viroid, Genomics, Humulus lupulus, Long non-coding RNAs, Plant defense, RNA-sequencing,
• MeSH
• Citrus * genetics   MeSH
• Humulus * genetics   MeSH
• Plant Bark MeSH
• Plant Diseases genetics   MeSH
• RNA, Long Noncoding * genetics   MeSH
• Gene Expression Profiling MeSH
• Viroids * genetics   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• RNA, Long Noncoding * 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.

• Keywords
• gene expression regulation, miRNA lncRNA., non-coding RNA,
• MeSH
• Humans MeSH
• MicroRNAs genetics   physiology   MeSH
• RNA, Untranslated genetics   physiology   MeSH
• Gene Expression Regulation genetics   physiology   MeSH
• RNA, Long Noncoding genetics   physiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• MicroRNAs MeSH
• RNA, Untranslated MeSH
• RNA, Long Noncoding MeSH