Special Issue "Gene Silencing"

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics".

Deadline for manuscript submissions: closed (15 May 2013)

Special Issue Editor

Guest Editor
Dr. Célia Baroux

Institute of Plant Biology, Basel-Zürich Plant Science Center, University of Zürich, Zollikerstr. 107, CH-8008 Zürich, Switzerland
Website | E-Mail
Interests: epigenetics; cytogenetics; chromatin dynamics; plant development

Special Issue Information

Dear Colleagues,

The development of multicellular organisms and the operation of complex cellular function requires not only perfect orchestration of gene expression but also a precise spatial and temporal control of gene silencing. Gene silencing mechanisms are diverse and exquisitely refined. These mechanisms operate at the transcriptional and post-transcriptional levels, or during meiosis; they use a variety of cellular components such as cis-DNA elements, chromatin modifications, small and non-coding RNAs and specific protein factors responsible for the initiation, operation and readout of silencing.
Common scenarios of gene silencing are found in plants, insects, worms and mammals. Yet each organism reveal specific adaptations and regulations. Those are important to elucidate, not only for philosophical purposes (with the meaning of studying and understanding general and fundamental problems) but also for medical or biotechnological applications.
This Special issue of "Genes" welcomes reviews and original papers covering recent research in gene silencing at the mechanistic and regulation levels in different organisms, but also research bridging gene silencing and cellular function, development or biotechnological applications.

Dr. Célia Baroux
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 800 CHF (Swiss Francs).

Keywords

  • gene silencing
  • genomic Imprinting
  • paramutation
  • transposon silencing
  • transgene silencing
  • position effect
  • RNA-directed DNA methylation
  • RNA interference
  • nonsense mediated decay
  • meiotic silencing of unpaired DNA

Published Papers (7 papers)

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Research

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Open AccessArticle Notch1 Activation Up-Regulates Pancreatic and Duodenal Homeobox-1
Genes 2013, 4(3), 358-374; doi:10.3390/genes4030358
Received: 14 May 2013 / Revised: 2 July 2013 / Accepted: 11 July 2013 / Published: 19 July 2013
Cited by 1 | PDF Full-text (1396 KB) | HTML Full-text | XML Full-text
Abstract
Transcription factor pancreatic and duodenal homeobox-1 (PDX-1) plays an essential role in pancreatic development, β-cell differentiation, maintenance of normal β-cell function and tumorigenesis. PDX-1 expression is tightly controlled through a variety of mechanisms under different cellular contexts. We report here that overexpression of
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Transcription factor pancreatic and duodenal homeobox-1 (PDX-1) plays an essential role in pancreatic development, β-cell differentiation, maintenance of normal β-cell function and tumorigenesis. PDX-1 expression is tightly controlled through a variety of mechanisms under different cellular contexts. We report here that overexpression of Notch1 intracellular domain (NICD), an activated form of Notch1, enhanced PDX-1 expression in both PDX-1 stable HEK293 cells and mouse insulinoma β-TC-6 cells, while NICD shRNA inhibited the enhancing effect. NICD-enhanced PDX-1 expression was accompanied by increased insulin expression/secretion and cell proliferation in β-TC-6 cells, which was reversed by NICD shRNA. Cre activation-induced specific expression of NICD in islet β cells of transgenic βNICD+/+ mice induced increased expression of PDX-1, insulin and proliferating cell nuclear antigen (PCNA) and decreased expression of p27 with accompanied fasting hyperinsulinemia and hypoglycemia and altered responses to intraperitoneal glucose tolerance test. Systemically delivered NICD shRNA suppressed islet expression of PDX-1 and reversed the hypoglycemia and hyperinsulinemia. Moreover, expression levels of NICD were correlated with those of PDX-1 in human pancreatic neuroendocrine tumor. Thus, Notch1 acts as a positive regulator for PDX-1 expression, cooperates with PDX-1 in the development of insulin overexpression and islet cell neoplasia and represents a potential therapeutic target for islet neoplasia. Full article
(This article belongs to the Special Issue Gene Silencing)
Open AccessCommunication RNAi-Mediated Gene Silencing in a Gonad Organ Culture to Study Sex Determination Mechanisms in Sea Turtle
Genes 2013, 4(2), 293-305; doi:10.3390/genes4020293
Received: 31 January 2013 / Revised: 15 May 2013 / Accepted: 20 May 2013 / Published: 7 June 2013
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Abstract
The autosomal Sry-related gene, Sox9, encodes a transcription factor, which performs an important role in testis differentiation in mammals. In several reptiles, Sox9 is differentially expressed in gonads, showing a significant upregulation during the thermo-sensitive period (TSP) at the male-promoting temperature,
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The autosomal Sry-related gene, Sox9, encodes a transcription factor, which performs an important role in testis differentiation in mammals. In several reptiles, Sox9 is differentially expressed in gonads, showing a significant upregulation during the thermo-sensitive period (TSP) at the male-promoting temperature, consistent with the idea that SOX9 plays a central role in the male pathway. However, in spite of numerous studies, it remains unclear how SOX9 functions during this event. In the present work, we developed an RNAi-based method for silencing Sox9 in an in vitro gonad culture system for the sea turtle, Lepidochelys olivacea. Gonads were dissected as soon as the embryos entered the TSP and were maintained in organ culture. Transfection of siRNA resulted in the decrease of both Sox9 mRNA and protein. Furthermore, we found coordinated expression patterns for Sox9 and the anti-Müllerian hormone gene, Amh, suggesting that SOX9 could directly or indirectly regulate Amh expression, as it occurs in mammals. These results demonstrate an in vitro method to knockdown endogenous genes in gonads from a sea turtle, which represents a novel approach to investigate the roles of important genes involved in sex determination or differentiation pathways in species with temperature-dependent sex determination. Full article
(This article belongs to the Special Issue Gene Silencing)
Figures

Open AccessArticle High SINE RNA Expression Correlates with Post-Transcriptional Downregulation of BRCA1
Genes 2013, 4(2), 226-243; doi:10.3390/genes4020226
Received: 28 March 2013 / Revised: 9 April 2013 / Accepted: 23 April 2013 / Published: 29 April 2013
PDF Full-text (447 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Short Interspersed Nuclear Elements (SINEs) are non-autonomous retrotransposons that comprise a large fraction of the human genome. SINEs are demethylated in human disease, but whether SINEs become transcriptionally induced and how the resulting transcripts may affect the expression of protein coding genes is
[...] Read more.
Short Interspersed Nuclear Elements (SINEs) are non-autonomous retrotransposons that comprise a large fraction of the human genome. SINEs are demethylated in human disease, but whether SINEs become transcriptionally induced and how the resulting transcripts may affect the expression of protein coding genes is unknown. Here, we show that downregulation of the mRNA of the tumor suppressor gene BRCA1 is associated with increased transcription of SINEs and production of sense and antisense SINE small RNAs. We find that BRCA1 mRNA is post-transcriptionally down-regulated in a Dicer and Drosha dependent manner and that expression of a SINE inverted repeat with sequence identity to a BRCA1 intron is sufficient for downregulation of BRCA1 mRNA. These observations suggest that transcriptional activation of SINEs could contribute to a novel mechanism of RNA mediated post-transcriptional silencing of human genes. Full article
(This article belongs to the Special Issue Gene Silencing)

Review

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Open AccessReview Gene Silencing in Crustaceans: From Basic Research to Biotechnologies
Genes 2013, 4(4), 620-645; doi:10.3390/genes4040620
Received: 17 May 2013 / Revised: 14 August 2013 / Accepted: 8 October 2013 / Published: 7 November 2013
Cited by 16 | PDF Full-text (613 KB) | HTML Full-text | XML Full-text
Abstract
Gene silencing through RNA interference (RNAi) is gaining momentum for crustaceans, both in basic research and for commercial development. RNAi has proven instrumental in a growing number of crustacean species, revealing the functionality of novel crustacean genes essential among others to development, growth,
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Gene silencing through RNA interference (RNAi) is gaining momentum for crustaceans, both in basic research and for commercial development. RNAi has proven instrumental in a growing number of crustacean species, revealing the functionality of novel crustacean genes essential among others to development, growth, metabolism and reproduction. Extensive studies have also been done on silencing of viral transcripts in crustaceans, contributing to the understanding of the defense mechanisms of crustaceans and strategies employed by viruses to overcome these. The first practical use of gene silencing in aquaculture industry has been recently achieved, through manipulation of a crustacean insulin-like androgenic gland hormone. This review summarizes the advancements in the use of RNAi in crustaceans, and assesses the advantages of this method, as well as the current hurdles that hinder its large-scale practice. Full article
(This article belongs to the Special Issue Gene Silencing)
Open AccessReview Nickel and Epigenetic Gene Silencing
Genes 2013, 4(4), 583-595; doi:10.3390/genes4040583
Received: 21 May 2013 / Revised: 11 October 2013 / Accepted: 17 October 2013 / Published: 25 October 2013
Cited by 8 | PDF Full-text (181 KB) | HTML Full-text | XML Full-text
Abstract
Insoluble nickel compounds are well-established human carcinogens. Occupational exposure to these compounds leads to increased incidence of lung and nasal cancer in nickel refinery workers. Apart from its weak mutagenic activity and hypoxia mimicking effect there is mounting experimental evidence indicating that epigenetic
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Insoluble nickel compounds are well-established human carcinogens. Occupational exposure to these compounds leads to increased incidence of lung and nasal cancer in nickel refinery workers. Apart from its weak mutagenic activity and hypoxia mimicking effect there is mounting experimental evidence indicating that epigenetic alteration plays an important role in nickel-induced carcinogenesis. Multiple epigenetic mechanisms have been identified to mediate nickel-induced gene silencing. Nickel ion is able to induce heterochromatinization by binding to DNA-histone complexes and initiating chromatin condensation. The enzymes required for establishing or removing epigenetic marks can be targeted by nickel, leading to altered DNA methylation and histone modification landscapes. The current review will focus on the epigenetic changes that contribute to nickel-induced gene silencing. Full article
(This article belongs to the Special Issue Gene Silencing)
Open AccessReview Antisense Gene Silencing: Therapy for Neurodegenerative Disorders?
Genes 2013, 4(3), 457-484; doi:10.3390/genes4030457
Received: 20 May 2013 / Revised: 11 July 2013 / Accepted: 13 August 2013 / Published: 10 September 2013
Cited by 4 | PDF Full-text (942 KB) | HTML Full-text | XML Full-text
Abstract
Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also
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Since the first reports that double-stranded RNAs can efficiently silence gene expression in C. elegans, the technology of RNA interference (RNAi) has been intensively exploited as an experimental tool to study gene function. With the subsequent discovery that RNAi could also be applied to mammalian cells, the technology of RNAi expanded from being a valuable experimental tool to being an applicable method for gene-specific therapeutic regulation, and much effort has been put into further refinement of the technique. This review will focus on how RNAi has developed over the years and how the technique is exploited in a pre-clinical and clinical perspective in relation to neurodegenerative disorders. Full article
(This article belongs to the Special Issue Gene Silencing)
Open AccessReview siRNA Treatment: “A Sword-in-the-Stone” for Acute Brain Injuries
Genes 2013, 4(3), 435-456; doi:10.3390/genes4030435
Received: 15 May 2013 / Revised: 17 August 2013 / Accepted: 22 August 2013 / Published: 5 September 2013
Cited by 5 | PDF Full-text (576 KB) | HTML Full-text | XML Full-text
Abstract
Ever since the discovery of small interfering ribonucleic acid (siRNA) a little over a decade ago, it has been highly sought after for its potential as a therapeutic agent for many diseases. In this review, we discuss the promising possibility of siRNA to
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Ever since the discovery of small interfering ribonucleic acid (siRNA) a little over a decade ago, it has been highly sought after for its potential as a therapeutic agent for many diseases. In this review, we discuss the promising possibility of siRNA to be used as a drug to treat acute brain injuries such as stroke and traumatic brain injury. First, we will give a brief and basic overview of the principle of RNA interference as an effective mechanism to decrease specific protein expression. Then, we will review recent in vivo studies describing siRNA research experiments/treatment options for acute brain diseases. Lastly, we will discuss the future of siRNA as a clinical therapeutic strategy against brain diseases and injuries, while addressing the current obstacles to effective brain delivery. Full article
(This article belongs to the Special Issue Gene Silencing)

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

 

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