Genomic Instability and Non-Coding RNA

A special issue of Non-Coding RNA (ISSN 2311-553X).

Deadline for manuscript submissions: closed (15 October 2018) | Viewed by 31601

Special Issue Editors

Department of Microbiology & Immunology, College of Physicians and Surgeons Columbia University 701W, 168th street HHSC910C, New York, NY 10032, USA
Interests: Long non-coding RNA; genomic instability; enhancers; superenhancers; 3D genomes; somatic mutations; genome rearrangements
Associate Research Scientist, Department of Biological Sciences, Columbia University, MC2411, 1212 Amsterdam Avenue, New York, NY 10027, USA
Interests: DNA damage, transcription regulation, Senataxin, R loops, neurodegenerative disorders, AOA2, ALS4

Special Issue Information

Dear Colleagues,

Intergenic and intragenic regions of the mammalian genome are organized inside topologically-associated regulatory domains (TADs) that express various types of noncoding RNAs (ncRNAs). These ncRNAs are associated with bi-directionally transcribed promoters, enhancers and intragenic antisense RNA expressing units. Recent studies have indicated these noncoding RNAs could also play a role in gene regulatory networks by controlling promoter and enhancer interactions and topology of higher-order chromatin structure.  However, the transcription and stabilization of these ncRNAs could also lead to genomic instability due to formation of deleterious secondary DNA structures, noncoding RNA associated DNA/RNA hybrid formation, and promote transcription complex stalling that eventually lead to collisions of transcription complexes with replisomes. Thus, ncRNA biogenesis and surveillance may play a vital role in determining the organization, function and stability of the mammalian genome. Finally, many noncoding RNAs that are able to survive the interrogation of the RNA surveillance machinery control gene expression via trans-acting regulatory mechanisms in the nucleus and cytoplasm of mammalian cells. In this Special Issue of Noncoding RNA we invite many experts in the field of RNA biology to present their point of view on various aspects of ncRNA transcription, function, regulation and surveillance.

Dr. Uttiya Basu
Dr. Patricia Richard
Guest Editors

Manuscript Submission Information

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Keywords

  • noncoding RNA
  • bidirectional transcription
  • long intergenic noncoding RNA
  • antisense RNA
  • enhancer–superenhancer, R-loops
  • DNA/RNA secondary structures
  • replisome/transcription complex collisions
  • DNA mutations
  • DNA translocations
  • DNA damage repair
  • histone and chromatin modifications
  • chromatin states
  • epigenetics

Published Papers (4 papers)

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Review

22 pages, 573 KiB  
Review
Mechanisms of Antisense Transcription Initiation with Implications in Gene Expression, Genomic Integrity and Disease Pathogenesis
by Priyanka Barman, Divya Reddy and Sukesh R. Bhaumik
Non-Coding RNA 2019, 5(1), 11; https://doi.org/10.3390/ncrna5010011 - 21 Jan 2019
Cited by 21 | Viewed by 5978
Abstract
Non-coding antisense transcripts arise from the strand opposite the sense strand. Over 70% of the human genome generates non-coding antisense transcripts while less than 2% of the genome codes for proteins. Antisense transcripts and/or the act of antisense transcription regulate gene expression and [...] Read more.
Non-coding antisense transcripts arise from the strand opposite the sense strand. Over 70% of the human genome generates non-coding antisense transcripts while less than 2% of the genome codes for proteins. Antisense transcripts and/or the act of antisense transcription regulate gene expression and genome integrity by interfering with sense transcription and modulating histone modifications or DNA methylation. Hence, they have significant pathological and physiological relevance. Indeed, antisense transcripts were found to be associated with various diseases including cancer, diabetes, cardiac and neurodegenerative disorders, and, thus, have promising potentials for prognostic and diagnostic markers and therapeutic development. However, it is not clearly understood how antisense transcription is initiated and epigenetically regulated. Such knowledge would provide new insights into the regulation of antisense transcription, and hence disease pathogenesis with therapeutic development. The recent studies on antisense transcription initiation and its epigenetic regulation, which are limited, are discussed here. Furthermore, we concisely describe how antisense transcription/transcripts regulate gene expression and genome integrity with implications in disease pathogenesis and therapeutic development. Full article
(This article belongs to the Special Issue Genomic Instability and Non-Coding RNA)
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17 pages, 702 KiB  
Review
Long Non-Coding RNAs in Obesity-Induced Cancer
by Mabel Yin-Chun Yau, Lu Xu, Chien-Ling Huang and Chi-Ming Wong
Non-Coding RNA 2018, 4(3), 19; https://doi.org/10.3390/ncrna4030019 - 28 Aug 2018
Cited by 19 | Viewed by 4223
Abstract
Many mechanisms of obesity-induced cancers have been proposed. However, it remains unclear whether or not long non-coding RNAs (lncRNAs) play any role in obesity-induced cancers. In this article, we briefly discuss the generally accepted hypotheses explaining the mechanisms of obesity-induced cancers, summarize the [...] Read more.
Many mechanisms of obesity-induced cancers have been proposed. However, it remains unclear whether or not long non-coding RNAs (lncRNAs) play any role in obesity-induced cancers. In this article, we briefly discuss the generally accepted hypotheses explaining the mechanisms of obesity-induced cancers, summarize the latest evidence for the expression of a number of well-known cancer-associated lncRNAs in obese subjects, and propose the potential contribution of lncRNAs to obesity-induced cancers. We hope this review can serve as an inspiration to scientists to further explore the regulatory roles of lncRNAs in the development of obesity-induced cancers. Those findings will be fundamental in the development of effective therapeutics or interventions to combat this life-threatening adverse effect of obesity. Full article
(This article belongs to the Special Issue Genomic Instability and Non-Coding RNA)
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15 pages, 3563 KiB  
Review
Strengths and Weaknesses of the Current Strategies to Map and Characterize R-Loops
by Vincent Vanoosthuyse
Non-Coding RNA 2018, 4(2), 9; https://doi.org/10.3390/ncrna4020009 - 27 Mar 2018
Cited by 49 | Viewed by 9598
Abstract
R-loops are evolutionarily conserved three-stranded structures that result from the formation of stable DNA:RNA hybrids in the genome. R-loops have attracted increasing interest in recent years as potent regulators of gene expression and genome stability. In particular, their strong association with severe replication [...] Read more.
R-loops are evolutionarily conserved three-stranded structures that result from the formation of stable DNA:RNA hybrids in the genome. R-loops have attracted increasing interest in recent years as potent regulators of gene expression and genome stability. In particular, their strong association with severe replication stress makes them potential oncogenic structures. Despite their importance, the rules that govern their formation and their dynamics are still controversial and an in-depth description of their direct impact on chromatin organization and DNA transactions is still lacking. To better understand the diversity of R-loop functions, reliable, accurate, and quantitative mapping techniques, as well as functional assays are required. Here, I review the different approaches that are currently used to do so and to highlight their individual strengths and weaknesses. In particular, I review the advantages and disadvantages of using the S9.6 antibody to map R-loops in vivo in an attempt to propose guidelines for best practices. Full article
(This article belongs to the Special Issue Genomic Instability and Non-Coding RNA)
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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 50 | Viewed by 11099
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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