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Background: The genetic code for every organism is stored in biomolecules the deoxyribonucleic acid (DNA) and the ribonucleic acid (RNA). In higher organisms, DNA is found inside the nucleus while RNA is found outside the nucleus. While gene, which is directly responsible for the coding of proteins which are needed by the organism, constitutes only around one per cent of DNA, the remaining 99 per cent is noncoding. Coding RNA generally refers to mRNA that encodes protein, noncoding RNAs  act as cellular regulators without encoding proteins. Main text: Although two-thirds of the human genome get transcribed, only 2% of the transcribed genome encodes proteins. It has been found that the remaining gets converted into long ncRNA and other ncRNAs. Noncoding RNA molecules known right from the early days of molecular biology are molecules like tRNA and rRNA. Long ncRNAs (lncRNA) were thought of as transcriptional noise even in the genomic era, but it has been found that they act as regulators at different levels of gene expression including chromatin organisation, transcriptional regulation and post-transcriptional control. This means that long ncRNAs control all stages of cell biogenesis and have critical roles in cell development and diseases. As much as they are vital to the development, evidence from research proves that mutations and dysregulations of these long ncRNA molecules are linked to diverse human diseases ranging from neuro-degeneration to cancers. Conclusion: The noncoding gene which was largely ignored in the initial days of molecular biology has come to the centre space after the prime role it occupies in the various stages of biogenesis of organisms has come to light. The study of such molecules is vital and central in molecular biology today and they are immensely researched in drug discovery too. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are membranous particles released by all cell types. Their role as functional carrier of bioactive molecules is boosted by cells that actively secrete them in biological fluids or in the intercellular space (interstitial EVs, iEVs). Here we have optimised a method for the isolation and characterization of zebrafish iEVs from whole melanoma tissues. Zebrafish melanoma iEVs are around 140 nm in diameter, as determined by nanoparticle tracking and transmission electron microscopy (TEM) analysis. Western blot analysis shows enrichment for CD63 and Alix in the iEV fraction, but not in melanoma cell lysates. Super resolution and confocal microscopy reveal that purified zebrafish iEVs are green fluorescent protein positive (GFP+), indicating that they integrate the oncogene GFP-HRASV12G used to induce melanoma in this model within their vesicular membrane or luminal content. Analysis of RNA-Seq data found 118 non-coding (nc)RNAs differentially distributed between zebrafish melanoma and their iEVs, with only 17 of them being selectively enriched in iEVs. Among these, the RNA components of RNAses P and MRP, which process ribosomal RNA precursors, mitochondrial RNAs, and some mRNAs, were enriched in zebrafish and human melanoma EVs, but not in iEVs extracted from brain tumours. We found that melanoma iEVs induce an inflammatory response when injected in larvae, with increased expression of interferon responsive genes, and this effect is reproduced by MRP- or P-RNAs injected into circulation. This suggests that zebrafish melanoma iEVs are a source of MRP- and P-RNAs that can trigger inflammation in cells of the innate immune system. [ABSTRACT FROM AUTHOR]

Background: Long non-coding RNAs (lncRNAs) represent a novel class of non-coding RNAs having a crucial role in many biological processes. The identification of long non-coding homologs among different species is essential to investigate such roles in model organisms as homologous genes tend to retain similar molecular and biological functions. Alignment–based metrics are able to effectively capture the conservation of transcribed coding sequences and then the homology of protein coding genes. However, unlike protein coding genes the poor sequence conservation of long non-coding genes makes the identification of their homologs a challenging task. Results: In this study we compare alignment–based and alignment–free string similarity metrics and look at promoter regions as a possible source of conserved information. We show that promoter regions encode relevant information for the conservation of long non-coding genes across species and that such information is better captured by alignment–free metrics. We perform a genome wide test of this hypothesis in human, mouse, and zebrafish. Conclusions: The obtained results persuaded us to postulate the new hypothesis that, unlike protein coding genes, long non-coding genes tend to preserve their regulatory machinery rather than their transcribed sequence. All datasets, scripts, and the prediction tools adopted in this study are available at https://github.com/bioinformatics-sannio/lncrna-homologs. [ABSTRACT FROM AUTHOR]

Bidirectional initiation of transcription by RNA polymerase II occurs prevalently at active promoters during protein-coding gene (PCG) expression. Upstream, antisense noncoding RNAs (ncRNAs) of differing lengths, stabilities and processings are being expressed from these promoters in concert with downstream, processive messenger RNA transcription. Although abundantly detected, the functional role and regulatory capacity of such transcripts have only been determined for individual cases. Long ncRNAs in general are reportedly able to regulate all steps of the gene expression process. Therefore, to get insight into the functionality of long ncRNAs transcribed bidirectionally from cancer-associated PCGs is of interest, as expression changes of tumor suppressor genes and oncogenes are prevalent in cancer. Here, we review the sources and characteristics of antisense transcription occurring at PCG loci in the human genome, and focus on the functional impact of bidirectional long ncRNA expression at cancer-associated PCGs. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) are becoming more prevalent in the cancer field arena, with functional roles in both oncogenic and onco-suppressive pathways. Despite their widespread aberrant expression in a range of human malignancies, the biological activities of the ncRNAs majority are unknown. All showed the involvement of the lncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT-AS1). Since NNT-AS1 influences cellular proliferation, invasion, migration, apoptosis, and metastasis, this lncRNA appears to be linked to deregulating the normal cellular processes driving malignancy. This was observed in breast cancer (BC), gastric cancer (GC), colorectal cancer (CRC), epithelial ovarian cancer (EOC), and hepatocellular carcinoma (HCC). The current narrative non-systematic review will discuss "the significance of lncRNAs in cancer", as well as "lncRNAs future potential application(s) as diagnostic or predictive biomarkers", therefore, comprising an opportunity as treatment target(s). The review will have a special emphasis on lncRNA NNT-AS1. [Display omitted] [ABSTRACT FROM AUTHOR]

The imprinted Airn macro long non-coding (lnc) RNA is an established example of a cis-silencing lncRNA. Airn expression is necessary to initiate paternal-specific silencing of the Igf2r gene, which is followed by gain of a somatic DNA methylation imprint on the silent Igf2r promoter. However, the developmental requirements for Airn initiation of silencing and the role of Airn or DNA methylation in maintaining stable Igf2r repression have not been investigated. Here, we use inducible systems to control Airn expression during mouse embryonic stem cell (ESC) differentiation. By turning Airn expression off during ESC differentiation, we show that continuous Airn expression is needed to maintain Igf2r silencing, but only until the paternal Igf2r promoter is methylated. By conditionally turning Airn expression on, we show that Airn initiation of Igf2r silencing is not limited to one developmental 'window of opportunity' and can be maintained in the absence of DNA methylation. Together, this study shows that Airn expression is both necessary and sufficient to silence Igf2r throughout ESC differentiation and that the somatic methylation imprint, although not required to initiate or maintain silencing, adds a secondary layer of repressive epigenetic information. [ABSTRACT FROM AUTHOR]

Abstract: Chromosome ends have been implicated in the default silencing of clonally variant gene families in the human malaria parasite Plasmodium falciparum. These chromosome regions are organized into heterochromatin, as defined by the presence of a repressive histone H3 lysine 9 trimethylated marker and heterochromatin protein 1. Here, we show that the non-coding subtelomeric region adjacent to virulence genes forms facultative heterochromatin in a cell cycle-dependent manner. We demonstrate that telomere-associated repeat elements (TAREs) and telomeres are transcribed as long non-coding RNAs (lncRNAs) during schizogony. Northern blot assays revealed two classes of lncRNAs: a ∼4-kb transcript composed of telomere sequences and a TARE-3 element, and a >6-kb transcript composed of 21-bp repeats from TARE-6. These lncRNAs are transcribed by RNA polymerase II as single-stranded molecules. RNA-FISH analysis showed that these lncRNAs form several nuclear foci during the schizont stage, whereas in the ring stage, they are located in a single perinuclear compartment that does not co-localize with any known nuclear subcompartment. Furthermore, the TARE-6 lncRNA is predicted to form a stable and repetitive hairpin structure that is able to bind histones. Consequently, the characterization of the molecular interactions of these lncRNAs with nuclear proteins may reveal novel modes of gene regulation and nuclear function in P. falciparum. [Copyright &y& Elsevier]

A large noncoding RNA called ANRIL (for antisense noncoding RNA in the INK4 locus) has been identified within the p15/CDKN2B-p16/CDKN2Ap14/ ARF gene cluster. While the exact role of ANRIL awaited further elucidation, common disease genomewide association studies (GWAS) have surprisingly identified the ANRIL gene as a genetic susceptibility locus shared associated by coronary disease, intracranial aneurysm and also type 2 diabetes. Expression studies have confirmed the coregulation of p15/CDKN2B, p16/ CDKN2A, p14/ARF, and ANRIL. Among the cluster, ANRIL expression showed the strongest association with the multiple phenotypes linked to the 9p21.3 region. More recent GWAS also identified ANRIL as a risk locus for gliomas and basal cell carcinomas in accordance with the princeps observation. Moreover, a mouse model has confirmed the pivotal role of ANRIL in regulation of CDKN2A/B expression through a cisacting mechanism and its implication in proliferation and senescence. The implication of ANRIL in cellular aging has provided an attractive unifying hypothesis to explain its association with various susceptibility risk factors. ANRIL identification emphasizes the underestimated role of long noncoding RNAs. Many GWAS have identified trait-associated SNPs that felt in noncoding genomic regions. It is conceivable to anticipate that long, noncoding RNAs will map to many of these "gene deserts." [ABSTRACT FROM AUTHOR]

Long non-coding RNA (long ncRNA) is a novel class of ncRNA that may be involved in critical cellular processes. A considerable number of mammalian long ncRNAs have now been isolated but only a small number of these nucleic acids have been functionally well characterized. In this study, to determine the structure, regulation and function of long ncRNA in pigs, TncRNA was isolated from this mammal and its potential function during pig foetus development was identified. We anticipated that this would provide new insights into functional genomic studies in the pig. Using LongSAGE libraries generated from Chinese indigenous Tongcheng and Landrace pigs at three prenatal stages, a novel porcine long ncRNA was identified, TncRNA, which was found to be differentially expressed during myogenesis. The full-length cDNA for this gene is 3409 bp, and it harbours a typical polyadenylation signal sequence located 18 bp upstream from the 3′ poly (A) tail. Genomic sequence analysis showed that pig TncRNA is alternatively spliced and several transcripts were detected. Using the INRA–University of Minnesota porcine radiation hybrid panel, TncRNA was assigned to SSC2 and found to be closely linked to the microsatellite marker SW256. Porcine TncRNA was found to be expressed in all tissues examined but in variable amounts. Comparisons between the expression profiles of TncRNA at different development stages in Tongcheng and Landrace pigs revealed up-regulation of this molecule in prenatal skeletal muscle, and differential expression in 90-day-old foetal skeletal muscle between these two pig breeds. This is the first report to describe a long ncRNA in pig. Moreover, the distinct expression pattern and structure of porcine TncRNA suggest that it performs complex and critical functions during foetal development. [ABSTRACT FROM AUTHOR]

Regulation of microRNA (miRNA) expression has been extensively studied with respect to colorectal cancer (CRC), since CRC is one of the leading causes of cancer mortality worldwide. Transcriptional control of miRNAs creating clusters can be, to some extent, estimated from cluster position on a chromosome. Levels of miRNAs are also controlled by miRNAs "sponging" by long non-coding RNAs (ncRNAs). Both types of miRNA regulation strongly influence their function. We focused on clusters of miRNAs found to be down-regulated in CRC, containing miR-1, let-7, miR-15, miR-16, miR-99, miR-100, miR-125, miR-133, miR-143, miR-145, miR-192, miR-194, miR-195, miR-206, miR-215, miR-302, miR-367 and miR-497 and analysed their genome position, regulation and functions. Only evidence provided with the use of CRC in vivo and/or in vitro models was taken into consideration. Comprehensive research revealed that down-regulated miRNA clusters in CRC are mostly located in a gene intron and, in a majority of cases, miRNA clusters possess cluster-specific transcriptional regulation. For all selected clusters, regulation mediated by long ncRNA was experimentally demonstrated in CRC, at least in one cluster member. Oncostatic functions were predominantly linked with the reviewed miRNAs, and their high expression was usually associated with better survival. These findings implicate the potential of down-regulated clusters in CRC to become promising multi-targets for therapeutic manipulation. [ABSTRACT FROM AUTHOR]