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Non-Coding RNA, Volume 4, Issue 1 (March 2018) – 8 articles

Cover Story (view full-size image): The nuclear RNA exosome regulates the metabolism of a huge plethora of RNA species. Recent studies have identified a number of co-factors that direct the exosome towards specific substrates. Moreover, in addition to its role in regulating the activity and maintaining the fidelity of gene expression, its physiological significance in multiple biological processes—such as DNA damage response, R-loop resolution, RNA export, translation, cell differentiation and virus infectivity—is gradually being understood. View this paper
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21 pages, 2067 KiB  
Review
RNA Surveillance by the Nuclear RNA Exosome: Mechanisms and Significance
by Koichi Ogami, Yaqiong Chen and James L. Manley
Non-Coding RNA 2018, 4(1), 8; https://doi.org/10.3390/ncrna4010008 - 11 Mar 2018
Cited by 52 | Viewed by 12312
Abstract
The nuclear RNA exosome is an essential and versatile machinery that regulates maturation and degradation of a huge plethora of RNA species. The past two decades have witnessed remarkable progress in understanding the whole picture of its RNA substrates and the structural basis [...] Read more.
The nuclear RNA exosome is an essential and versatile machinery that regulates maturation and degradation of a huge plethora of RNA species. The past two decades have witnessed remarkable progress in understanding the whole picture of its RNA substrates and the structural basis of its functions. In addition to the exosome itself, recent studies focusing on associated co-factors have been elucidating how the exosome is directed towards specific substrates. Moreover, it has been gradually realized that loss-of-function of exosome subunits affect multiple biological processes, such as the DNA damage response, R-loop resolution, maintenance of genome integrity, RNA export, translation, and cell differentiation. In this review, we summarize the current knowledge of the mechanisms of nuclear exosome-mediated RNA metabolism and discuss their physiological significance. Full article
(This article belongs to the Special Issue Genomic Instability and Non-Coding RNA)
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10 pages, 203 KiB  
Review
The Role of Long Non-Coding RNAs in Osteosarcoma
by Maria Anna Smolle and Martin Pichler
Non-Coding RNA 2018, 4(1), 7; https://doi.org/10.3390/ncrna4010007 - 8 Mar 2018
Cited by 56 | Viewed by 4156
Abstract
Long non-coding RNAs (lncRNAs) constitute non-protein coding transcripts with a size > than 200 nucleotides. They are involved in many cellular processes, such as chromatin remodelling, transcription, and gene expression. They play a role in the development, progression, and invasion of many human [...] Read more.
Long non-coding RNAs (lncRNAs) constitute non-protein coding transcripts with a size > than 200 nucleotides. They are involved in many cellular processes, such as chromatin remodelling, transcription, and gene expression. They play a role in the development, progression, and invasion of many human cancers, including osteosarcoma. This rare tumor entity predominantly arises in children and young adults. Treatment consists of polychemotherapy and surgical resection, increasing survival rates up to 60%. In the present review, the role of lncRNAs with prognostic, predictive, therapeutic, and diagnostic significance in osteosarcoma is discussed. Moreover, their potential application in clinical practice is highlighted. Full article
(This article belongs to the Section Long Non-Coding RNA)
15 pages, 4690 KiB  
Article
Sponge Long Non-Coding RNAs Are Expressed in Specific Cell Types and Conserved Networks
by Federico Gaiti, William L. Hatleberg, Miloš Tanurdžić and Bernard M. Degnan
Non-Coding RNA 2018, 4(1), 6; https://doi.org/10.3390/ncrna4010006 - 7 Mar 2018
Cited by 8 | Viewed by 5385
Abstract
Although developmental regulation by long non-coding RNAs (lncRNAs) appears to be a widespread feature amongst animals, the origin and level of evolutionary conservation of this mode of regulation remain unclear. We have previously demonstrated that the sponge Amphimedon queenslandica—a morphologically-simple animal—developmentally expresses [...] Read more.
Although developmental regulation by long non-coding RNAs (lncRNAs) appears to be a widespread feature amongst animals, the origin and level of evolutionary conservation of this mode of regulation remain unclear. We have previously demonstrated that the sponge Amphimedon queenslandica—a morphologically-simple animal—developmentally expresses an array of lncRNAs in manner akin to more complex bilaterians (insects + vertebrates). Here, we first show that Amphimedon lncRNAs are expressed in specific cell types in larvae, juveniles and adults. Thus, as in bilaterians, sponge developmental regulation involves the dynamic, cell type- and context-specific regulation of specific lncRNAs. Second, by comparing gene co-expression networks between Amphimedon queenslandica and Sycon ciliatum—a distantly-related calcisponge—we identify several putative co-expression modules that appear to be shared in sponges; these network-embedded sponge lncRNAs have no discernable sequence similarity. Together, these results suggest sponge lncRNAs are developmentally regulated and operate in conserved gene regulatory networks, as appears to be the case in more complex bilaterians. Full article
(This article belongs to the Special Issue Non-Coding RNAs, from an Evolutionary Perspective)
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8 pages, 2804 KiB  
Communication
miRNAtools: Advanced Training Using the miRNA Web of Knowledge
by Ewa Ł. Stępień, Marina C. Costa and Francisco J. Enguita
Non-Coding RNA 2018, 4(1), 5; https://doi.org/10.3390/ncrna4010005 - 16 Feb 2018
Cited by 5 | Viewed by 5755
Abstract
Micro-RNAs (miRNAs) are small non-coding RNAs that act as negative regulators of the genomic output. Their intrinsic importance within cell biology and human disease is well known. Their mechanism of action based on the base pairing binding to their cognate targets have helped [...] Read more.
Micro-RNAs (miRNAs) are small non-coding RNAs that act as negative regulators of the genomic output. Their intrinsic importance within cell biology and human disease is well known. Their mechanism of action based on the base pairing binding to their cognate targets have helped the development not only of many computer applications for the prediction of miRNA target recognition but also of specific applications for functional assessment and analysis. Learning about miRNA function requires practical training in the use of specific computer and web-based applications that are complementary to wet-lab studies. In order to guide the learning process about miRNAs, we have created miRNAtools (http://mirnatools.eu), a web repository of miRNA tools and tutorials. This article compiles tools with which miRNAs and their regulatory action can be analyzed and that function to collect and organize information dispersed on the web. The miRNAtools website contains a collection of tutorials that can be used by students and tutors engaged in advanced training courses. The tutorials engage in analyses of the functions of selected miRNAs, starting with their nomenclature and genomic localization and finishing with their involvement in specific cellular functions. Full article
(This article belongs to the Collection Non-Coding RNA Methods)
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8 pages, 2213 KiB  
Article
Unravelling the Long Non-Coding RNA Profile of Undifferentiated Large Cell Lung Carcinoma
by Sudhanshu Shukla
Non-Coding RNA 2018, 4(1), 4; https://doi.org/10.3390/ncrna4010004 - 5 Feb 2018
Cited by 4 | Viewed by 4217
Abstract
Undifferentiated large cell lung carcinoma (LCLC) accounts for 2.9–9% of total lung cancers. Recently, RNA-seq based studies have revealed major genomic aberrations in LCLC. In this study, we aim to identify long non-coding RNAs (LncRNAs) expression pattern specific to LCLC. The RNA-seq profile [...] Read more.
Undifferentiated large cell lung carcinoma (LCLC) accounts for 2.9–9% of total lung cancers. Recently, RNA-seq based studies have revealed major genomic aberrations in LCLC. In this study, we aim to identify long non-coding RNAs (LncRNAs) expression pattern specific to LCLC. The RNA-seq profile of LCLC and other non-small cell lung carcinoma (NSCLC) was downloaded from Gene Expression Omnibus (GEO) and analyzed. Using 10 LCLC samples, we found that 18% of all the annotated LncRNAs are expressed in LCLC samples. Among 1794 expressed LncRNAs, 11 were overexpressed and 14 were downregulated in LCLC compared to normal samples. Based on receiver operating characteristic (ROC) analysis, we showed that the top five differentially expressed LncRNAs were able to differentiate between LCLC and normal samples with high sensitivity and specificity. Guilt by association analysis using genes correlating with differentially expressed LncRNAs identified several cancer-associated pathways, suggesting the role of these deregulated LncRNA in LCLC biology. We also identified the LncRNA differentially expressed in LCLC compared to lung squamous carcinoma (LUSC) and Lung-adenocarcinoma (LUAD). We found that LCLC sample showed more deregulated LncRNA in LUSC than LUAD. Interestingly, LCLC had more downregulated LncRNA compared to LUAD and LUSC. Our study provides novel insight into LncRNA deregulation in LCLC. This study also finds tools to diagnose LCLC and differentiate LCLC with other Non-Small Cell Lung Cancer. Full article
(This article belongs to the Section Long Non-Coding RNA)
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30 pages, 2576 KiB  
Review
Besides Pathology: Long Non-Coding RNA in Cell and Tissue Homeostasis
by Amanda Salviano-Silva, Sara Cristina Lobo-Alves, Rodrigo Coutinho de Almeida, Danielle Malheiros and Maria Luiza Petzl-Erler
Non-Coding RNA 2018, 4(1), 3; https://doi.org/10.3390/ncrna4010003 - 30 Jan 2018
Cited by 110 | Viewed by 12364
Abstract
A significant proportion of mammalian genomes corresponds to genes that transcribe long non-coding RNAs (lncRNAs). Throughout the last decade, the number of studies concerning the roles played by lncRNAs in different biological processes has increased considerably. This intense interest in lncRNAs has produced [...] Read more.
A significant proportion of mammalian genomes corresponds to genes that transcribe long non-coding RNAs (lncRNAs). Throughout the last decade, the number of studies concerning the roles played by lncRNAs in different biological processes has increased considerably. This intense interest in lncRNAs has produced a major shift in our understanding of gene and genome regulation and structure. It became apparent that lncRNAs regulate gene expression through several mechanisms. These RNAs function as transcriptional or post-transcriptional regulators through binding to histone-modifying complexes, to DNA, to transcription factors and other DNA binding proteins, to RNA polymerase II, to mRNA, or through the modulation of microRNA or enzyme function. Often, the lncRNA transcription itself rather than the lncRNA product appears to be regulatory. In this review, we highlight studies identifying lncRNAs in the homeostasis of various cell and tissue types or demonstrating their effects in the expression of protein-coding or other non-coding RNA genes. Full article
(This article belongs to the Section Long Non-Coding RNA)
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2 pages, 280 KiB  
Editorial
Acknowledgement to Reviewers of Non-Coding RNA in 2017
by Non-Coding RNA Editorial Office
Non-Coding RNA 2018, 4(1), 2; https://doi.org/10.3390/ncrna4010002 - 23 Jan 2018
Viewed by 2490
Abstract
Peer review is an essential part in the publication process, ensuring that Non-Coding RNA maintains high quality standards for its published papers.[...] Full article
2205 KiB  
Article
A Novel Long Non-Coding RNA in the hTERT Promoter Region Regulates hTERT Expression
by Sanandan Malhotra, Mallory A. Freeberg, Shelby J. Winans, James Taylor and Karen L. Beemon
Non-Coding RNA 2018, 4(1), 1; https://doi.org/10.3390/ncrna4010001 - 29 Dec 2017
Cited by 26 | Viewed by 5166
Abstract
A novel antisense transcript was identified in the human telomerase reverse transcriptase (hTERT) promoter region, suggesting that the hTERT promoter is bidirectional. This transcript, named hTERT antisense promoter-associated (hTAPAS) RNA, is a 1.6 kb long non-coding RNA. hTAPAS transcription [...] Read more.
A novel antisense transcript was identified in the human telomerase reverse transcriptase (hTERT) promoter region, suggesting that the hTERT promoter is bidirectional. This transcript, named hTERT antisense promoter-associated (hTAPAS) RNA, is a 1.6 kb long non-coding RNA. hTAPAS transcription is initiated 167 nucleotides upstream of the hTERT transcription start site and is present in both the nucleus and the cytoplasm. Surprisingly, we observed that a large fraction of the hTERT polyadenylated RNA is localized in the nucleus, suggesting this might be an additional means of regulating the cellular abundance of hTERT protein. Both hTAPAS and hTERT are expressed in immortalized B-cells and human embryonic stem cells but are not detected in normal somatic cells. hTAPAS expression inversely correlates with hTERT expression in different types of cancer samples. Moreover, hTAPAS expression is not promoted by an hTERT promoter mutation (-124 C>T). Antisense-oligonucleotide mediated knockdown of hTAPAS results in an increase in hTERT expression. Conversely, ectopic overexpression of hTAPAS down regulates hTERT expression, suggesting a negative role in hTERT gene regulation. These observations provide insights into hTAPAS as a novel player that negatively regulates hTERT expression and may be involved in telomere length homeostasis. Full article
(This article belongs to the Section Long Non-Coding RNA)
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