Long Noncoding RNAs in Disease

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (28 February 2021) | Viewed by 14377

Special Issue Editor


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Guest Editor
Klaus Tschira Institute for Computational Cardiology, University Hospital Heidelberg, Heidelberg, Germany
Interests: RNA modifications; RNA-RNA and RNA-protein interactions; RNA splicing and Circular RNAs; Control of translation; RNA turnover; Medical Informatics; Data integration (OMICS & clinical data)

Special Issue Information

Dear Colleagues,

The first two decades of the 21st century have brought about a major change in how RNA molecules are regarded in molecular biology and biomedicine. For a long time, RNA had been primarily considered as an inert carrier of information that is the template for protein translation and a component of the translation machinery (tRNA/rRNA). Interestingly, the non-protein coding component of the transcriptome shows greater tissue and context specific expression patterns than the coding genome and plays an important role in phenotypic variation between individuals.

Specifically, non-coding RNA polymerase 2 transcripts of size greater than 200 base pairs are classified as long non-coding RNAs (lncRNAs) and received a lot of attention with the emergence of the first phenotypes (e.g., in neurodegenerative, cardiovascular diseases and cancer). LncRNAs encompass mainly long intragenic non-coding RNAs (intronic and antisense) and long intergenic noncoding RNAs (lincRNA).

This Special Issue on Long Noncoding RNAs in Disease aims to promote the research on the understanding of molecular mechanisms and functions of lncRNAs across all disease entities. Contributions on the prognostic and diagnostic value of lncRNA species will be considered too. In summary, we welcome contributions from all relevant fields, ranging from computational biology, molecular biology to biomedicine.

Prof. Dr. rer. nat. Christoph Dieterich
Guest Editor

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Keywords

  • Cancer
  • Cardiovascular disease
  • Neurodegeneration
  • RNA biology
  • Bioinformatics
  • Transcription
  • Splicing
  • Antisense
  • Enhancer
  • Chromatin

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Published Papers (4 papers)

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Research

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6 pages, 4885 KiB  
Article
DiseaseLinc: Disease Enrichment Analysis of Sets of Differentially Expressed LincRNAs
by Piyush More, Sweta Talyan, Jean-Fred Fontaine, Enrique M. Muro and Miguel A. Andrade-Navarro
Cells 2021, 10(4), 751; https://doi.org/10.3390/cells10040751 - 29 Mar 2021
Viewed by 2282
Abstract
Long intergenic non-coding RNAs (LincRNAs) are long RNAs that do not encode proteins. Functional evidence is lacking for most of them. Their biogenesis is not well-known, but it is thought that many lincRNAs originate from genomic duplication of coding material, resulting in pseudogenes, [...] Read more.
Long intergenic non-coding RNAs (LincRNAs) are long RNAs that do not encode proteins. Functional evidence is lacking for most of them. Their biogenesis is not well-known, but it is thought that many lincRNAs originate from genomic duplication of coding material, resulting in pseudogenes, gene copies that lose their original function and can accumulate mutations. While most pseudogenes eventually stop producing a transcript and become erased by mutations, many of these pseudogene-based lincRNAs keep similarity to the parental gene from which they originated, possibly for functional reasons. For example, they can act as decoys for miRNAs targeting the parental gene. Enrichment analysis of function is a powerful tool to discover the functional effects of a treatment producing differential expression of transcripts. However, in the case of lincRNAs, since their function is not easy to define experimentally, such a tool is lacking. To address this problem, we have developed an enrichment analysis tool that focuses on lincRNAs exploiting their functional association, using as a proxy function that of the parental genes and has a focus on human diseases. Full article
(This article belongs to the Special Issue Long Noncoding RNAs in Disease)
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15 pages, 2532 KiB  
Article
CALINCA—A Novel Pipeline for the Identification of lncRNAs in Podocyte Disease
by Sweta Talyan, Samantha Filipów, Michael Ignarski, Magdalena Smieszek, He Chen, Lucas Kühne, Linus Butt, Heike Göbel, K. Johanna R. Hoyer-Allo, Felix C. Koehler, Janine Altmüller, Paul Brinkkötter, Bernhard Schermer, Thomas Benzing, Martin Kann, Roman-Ulrich Müller and Christoph Dieterich
Cells 2021, 10(3), 692; https://doi.org/10.3390/cells10030692 - 20 Mar 2021
Cited by 3 | Viewed by 4304
Abstract
Diseases of the renal filtration unit—the glomerulus—are the most common cause of chronic kidney disease. Podocytes are the pivotal cell type for the function of this filter and focal-segmental glomerulosclerosis (FSGS) is a classic example of a podocytopathy leading to proteinuria and glomerular [...] Read more.
Diseases of the renal filtration unit—the glomerulus—are the most common cause of chronic kidney disease. Podocytes are the pivotal cell type for the function of this filter and focal-segmental glomerulosclerosis (FSGS) is a classic example of a podocytopathy leading to proteinuria and glomerular scarring. Currently, no targeted treatment of FSGS is available. This lack of therapeutic strategies is explained by a limited understanding of the defects in podocyte cell biology leading to FSGS. To date, most studies in the field have focused on protein-coding genes and their gene products. However, more than 80% of all transcripts produced by mammalian cells are actually non-coding. Here, long non-coding RNAs (lncRNAs) are a relatively novel class of transcripts and have not been systematically studied in FSGS to date. The appropriate tools to facilitate lncRNA research for the renal scientific community are urgently required due to a row of challenges compared to classical analysis pipelines optimized for coding RNA expression analysis. Here, we present the bioinformatic pipeline CALINCA as a solution for this problem. CALINCA automatically analyzes datasets from murine FSGS models and quantifies both annotated and de novo assembled lncRNAs. In addition, the tool provides in-depth information on podocyte specificity of these lncRNAs, as well as evolutionary conservation and expression in human datasets making this pipeline a crucial basis to lncRNA studies in FSGS. Full article
(This article belongs to the Special Issue Long Noncoding RNAs in Disease)
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Review

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20 pages, 3715 KiB  
Review
Not So Dead Genes—Retrocopies as Regulators of Their Disease-Related Progenitors and Hosts
by Joanna Ciomborowska-Basheer, Klaudia Staszak, Magdalena Regina Kubiak and Izabela Makałowska
Cells 2021, 10(4), 912; https://doi.org/10.3390/cells10040912 - 15 Apr 2021
Cited by 9 | Viewed by 3439
Abstract
Retroposition is RNA-based gene duplication leading to the creation of single exon nonfunctional copies. Nevertheless, over time, many of these duplicates acquire transcriptional capabilities. In human in most cases, these so-called retrogenes do not code for proteins but function as regulatory long noncoding [...] Read more.
Retroposition is RNA-based gene duplication leading to the creation of single exon nonfunctional copies. Nevertheless, over time, many of these duplicates acquire transcriptional capabilities. In human in most cases, these so-called retrogenes do not code for proteins but function as regulatory long noncoding RNAs (lncRNAs). The mechanisms by which they can regulate other genes include microRNA sponging, modulation of alternative splicing, epigenetic regulation and competition for stabilizing factors, among others. Here, we summarize recent findings related to lncRNAs originating from retrocopies that are involved in human diseases such as cancer and neurodegenerative, mental or cardiovascular disorders. Special attention is given to retrocopies that regulate their progenitors or host genes. Presented evidence from the literature and our bioinformatics analyses demonstrates that these retrocopies, often described as unimportant pseudogenes, are significant players in the cell’s molecular machinery. Full article
(This article belongs to the Special Issue Long Noncoding RNAs in Disease)
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16 pages, 1260 KiB  
Review
Propagation and Maintenance of Cancer Stem Cells: A Major Influence of the Long Non-Coding RNA H19
by Clément Lecerf, Evodie Peperstraete, Xuefen Le Bourhis and Eric Adriaenssens
Cells 2020, 9(12), 2613; https://doi.org/10.3390/cells9122613 - 5 Dec 2020
Cited by 18 | Viewed by 3640
Abstract
Cancer stem cells (CSCs) represent a rare population of tumor cells that exhibit stem cell properties with the abilities of self-renewal and differentiation. These cells are now widely accepted to be responsible for tumor initiation, development, resistance to conventional therapies, and recurrence. Thus, [...] Read more.
Cancer stem cells (CSCs) represent a rare population of tumor cells that exhibit stem cell properties with the abilities of self-renewal and differentiation. These cells are now widely accepted to be responsible for tumor initiation, development, resistance to conventional therapies, and recurrence. Thus, a better understanding of the molecular mechanisms involved in the control of CSCs is essential to improve patient management in terms of diagnostics and therapies. CSCs are regulated by signals of the tumor microenvironment as well as intrinsic genetic and epigenetic modulators. H19, the first identified lncRNA is involved in the development and progression of many different cancer types. Recently, H19 has been demonstrated to be implicated in the regulation of CSCs in different types of cancers. The aim of this review is to provide an overview of the role and mechanisms of action of H19 in the regulation of CSCs. We summarize how H19 may regulate CSC division and cancer cell reprogramming, thus affecting metastasis and drug resistance. We also discuss the potential clinical implications of H19. Full article
(This article belongs to the Special Issue Long Noncoding RNAs in Disease)
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