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Special Issue "Non-Coding RNAs"

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry, Molecular Biology and Biophysics".

Deadline for manuscript submissions: closed (31 October 2011)

Special Issue Editor

Guest Editor
Prof. Dr. Constantinos Stathopoulos (Website)

Department of Biochemistry, School of Medicine, University of Patras, 1 Asklipiou st., 26504 Patras, Greece
Fax: +30 2610 969167
Interests: tRNA; mRNA; riboswitches; antibiotics; aminoacyl-tRNA synthetases; ribonucleases; translation; ribosome; tRFs

Special Issue Information

Dear Colleagues,

During recent years, a remarkable expansion of the “RNA world” members has been observed with the discovery and characterization of many elusive, so far, RNA molecules of various sizes and regulatory roles, in both eukaryotes and bacteria. In the dawn of this new RNA era, the term “non-coding RNAs” represents not only molecules such as tRNAs, rRNAs and snoRNAs, that cannot be translated into proteins. Instead, it additionally includes a variety of prominent RNA molecules that play distinct and critical roles within the cell. In eukaryotes, these novel members are represented by numerous microRNAs, siRNAs, piRNAs and long non-coding RNAs, that exhibit trans-acting antisense modulating properties. Today, we know that they modulate gene expression by interfering in post-transcriptional level. Moreover, RNA interference-based methodologies have provided the means of studying gene expression at a glance, both in vitro and in vivo, and they have emerged as very delicate and promising therapeutic strategies. In bacteria, the new members are represented by many regulatory RNAs of various sizes, which are also responsible for essential cellular responses. These key elements, can either be embedded in the 5’ end of mRNAs (i.e. riboswitches), they can be small RNAs that act in trans by targeting proteins or RNAs, they can be long antisense RNA modulators (CRISPR RNAs) or they may even have intrinsic activity (like RNase P ribozyme). Whatever their origin, size, structure or specific role, it is more than evident that non-coding RNAs represent a dynamic and expanding family of essential molecules, some of them with deep evolutionary history. Moreover, they are established as valuable novel tools with biotechnological applications or/and targets for combating disease or pathogens. Their discovery and study has great impact not only in the way we approach specific cellular processes today, but also in the way we understand the evolution of life itself.

Prof. Dr. Constantinos Stathopoulos
Guest Editor

Keywords

  • tRNA
  • rRNA
  • snoRNA
  • ribozyme
  • microRNA
  • siRNA
  • piRNA
  • riboswitch
  • sRNA
  • CRISPR RNA

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Published Papers (12 papers)

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Research

Jump to: Review

Open AccessArticle ACVR1, a Therapeutic Target of Fibrodysplasia Ossificans Progressiva, Is Negatively Regulated by miR-148a
Int. J. Mol. Sci. 2012, 13(2), 2063-2077; doi:10.3390/ijms13022063
Received: 4 November 2011 / Revised: 3 February 2012 / Accepted: 7 February 2012 / Published: 15 February 2012
Cited by 17 | PDF Full-text (364 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder of skeletal malformations and progressive extraskeletal ossification. There is still no effective treatment for FOP. All FOP individuals harbor conserved point mutations in ACVR1 gene that are thought to cause ACVR1 constitutive activation [...] Read more.
Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder of skeletal malformations and progressive extraskeletal ossification. There is still no effective treatment for FOP. All FOP individuals harbor conserved point mutations in ACVR1 gene that are thought to cause ACVR1 constitutive activation and activate BMP signal pathway. The constitutively active ACVR1 is also found to be able to cause endothelial-to-mesenchymal transition (EndMT) in endothelial cells, which may cause the formation of FOP lesions. MicroRNAs (miRNAs) play an essential role in regulating cell differentiation. Here, we verified that miR-148a directly targeted the 3' UTR of ACVR1 mRNA by reporter gene assays and mutational analysis at the miRNA binding sites, and inhibited ACVR1 both at the protein level and mRNA level. Further, we verified that miR-148a could inhibit the mRNA expression of the Inhibitor of DNA binding (Id) gene family thereby suppressing the BMP signaling pathway. This study suggests miR-148a is an important mediator of ACVR1, thus offering a new potential target for the development of therapeutic agents against FOP. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
Open AccessArticle MetastamiRs: Non-Coding MicroRNAs Driving Cancer Invasion and Metastasis
Int. J. Mol. Sci. 2012, 13(2), 1347-1379; doi:10.3390/ijms13021347
Received: 28 November 2011 / Revised: 9 January 2012 / Accepted: 9 January 2012 / Published: 27 January 2012
Cited by 14 | PDF Full-text (1073 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that function as negative regulators of gene expression by either inhibiting translation or inducing deadenylation-dependent degradation of target transcripts. Notably, deregulation of miRNAs expression is associated with the initiation and progression of human [...] Read more.
MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that function as negative regulators of gene expression by either inhibiting translation or inducing deadenylation-dependent degradation of target transcripts. Notably, deregulation of miRNAs expression is associated with the initiation and progression of human cancers where they act as oncogenes or tumor suppressors contributing to tumorigenesis. Abnormal miRNA expression may provide potential diagnostic and prognostic tumor biomarkers and new therapeutic targets in cancer. Recently, several miRNAs have been shown to initiate invasion and metastasis by targeting multiple proteins that are major players in these cellular events, thus they have been denominated as metastamiRs. Here, we present a review of the current knowledge of miRNAs in cancer with a special focus on metastamiRs. In addition we discuss their potential use as novel specific markers for cancer progression. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
Open AccessArticle microRNA Response to Listeria monocytogenes Infection in Epithelial Cells
Int. J. Mol. Sci. 2012, 13(1), 1173-1185; doi:10.3390/ijms13011173
Received: 2 December 2011 / Revised: 5 January 2012 / Accepted: 13 January 2012 / Published: 20 January 2012
Cited by 22 | PDF Full-text (354 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
microRNAs represent a family of very small non-coding RNAs that control several physiologic and pathologic processes, including host immune response and cancer by antagonizing a number of target mRNAs. There is limited knowledge about cell expression and the regulatory role of microRNAs [...] Read more.
microRNAs represent a family of very small non-coding RNAs that control several physiologic and pathologic processes, including host immune response and cancer by antagonizing a number of target mRNAs. There is limited knowledge about cell expression and the regulatory role of microRNAs following bacterial infections. We investigated whether infection with a Gram-positive bacterium leads to altered expression of microRNAs involved in the host cell response in epithelial cells. Caco-2 cells were infected with Listeria monocytogenes EGD-e, a mutant strain (∆inlAB or ∆hly) or incubated with purified listeriolysin (LLO). Total RNA was isolated and microRNA and target gene expression was compared to the expression in non-infected cells using microRNA microarrays and qRT-PCR. We identified and validated five microRNAs (miR-146b, miR-16, let-7a1, miR-145 and miR-155) that were significantly deregulated following listerial infection. We show that expression patterns of particular microRNAs strongly depend on pathogen localization and the presence of bacterial effector proteins. Strikingly, miR-155 which was shown to have an important role in inflammatory responses during infection was induced by wild-type bacteria, by LLO-deficient bacteria and following incubation with purified LLO. It was downregulated following ∆inlAB infection indicating a new potent role for internalins in listerial pathogenicity and miRNA regulation. Concurrently, we observed differences in target transcript expression of the investigated miRNAs. We provide first evidence that L. monocytogenes infection leads to deregulation of a set of microRNAs with important roles in host response. Distinct microRNA expression depends on both LLO and pathogen localization. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
Open AccessArticle Inference of Gene Regulation via miRNAs During ES Cell Differentiation Using MiRaGE Method
Int. J. Mol. Sci. 2011, 12(12), 9265-9276; doi:10.3390/ijms12129265
Received: 24 October 2011 / Revised: 22 November 2011 / Accepted: 29 November 2011 / Published: 12 December 2011
Cited by 6 | PDF Full-text (321 KB) | HTML Full-text | XML Full-text
Abstract
MicroRNA (miRNA) is a critical regulator of cell growth, differentiation, and development. To identify important miRNAs in a biological process, many bioinformatical tools have been developed. We have developed MiRaGE (MiRNA Ranking by Gene Expression) method to infer the regulation of gene [...] Read more.
MicroRNA (miRNA) is a critical regulator of cell growth, differentiation, and development. To identify important miRNAs in a biological process, many bioinformatical tools have been developed. We have developed MiRaGE (MiRNA Ranking by Gene Expression) method to infer the regulation of gene expression by miRNAs from changes of gene expression profiles. The method does not require precedent array normalization. We applied the method to elucidate possibly important miRNAs during embryonic stem (ES) cell differentiation to neuronal cells and we infer that certain miRNAs, including miR-200 family, miR-429, miR-302 family, and miR-17-92 cluster members may be important to the maintenance of undifferentiated status in ES cells. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
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Open AccessArticle Genetic Association and Altered Gene Expression of Mir-155 in Multiple Sclerosis Patients
Int. J. Mol. Sci. 2011, 12(12), 8695-8712; doi:10.3390/ijms12128695
Received: 19 September 2011 / Revised: 31 October 2011 / Accepted: 22 November 2011 / Published: 1 December 2011
Cited by 37 | PDF Full-text (423 KB) | HTML Full-text | XML Full-text
Abstract
Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system characterized by chronic inflammation, demyelination, and axonal damage. As microRNA (miRNA)-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response, miRNA deregulation may [...] Read more.
Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system characterized by chronic inflammation, demyelination, and axonal damage. As microRNA (miRNA)-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response, miRNA deregulation may result in defects in immune tolerance. In this frame, we sought to explore the possible involvement of miRNAs in MS pathogenesis by monitoring the differential expression of 22 immunity-related miRNAs in peripheral blood mononuclear cells of MS patients and healthy controls, by using a microbead-based technology. Three miRNAs resulted >2 folds up-regulated in MS vs controls, whereas none resulted down-regulated. Interestingly, the most up-regulated miRNA (mir-155; fold change = 3.30; P = 0.013) was previously reported to be up-regulated also in MS brain lesions. Mir-155 up-regulation was confirmed by qPCR experiments. The role of mir-155 in MS susceptibility was also investigated by genotyping four single nucleotide polymorphisms (SNPs) mapping in the mir-155 genomic region. A haplotype of three SNPs, corresponding to a 12-kb region encompassing the last exon of BIC (the B-cell Integration Cluster non-coding RNA, from which mir-155 is processed), resulted associated with the disease status (P = 0.035; OR = 1.36, 95% CI = 1.05–1.77), suggesting that this locus strongly deserves further investigations. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
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Review

Jump to: Research

Open AccessReview Non-Coding RNAs: Functional Aspects and Diagnostic Utility in Oncology
Int. J. Mol. Sci. 2013, 14(3), 4934-4968; doi:10.3390/ijms14034934
Received: 10 December 2012 / Revised: 9 February 2013 / Accepted: 18 February 2013 / Published: 1 March 2013
Cited by 18 | PDF Full-text (372 KB) | HTML Full-text | XML Full-text
Abstract
Noncoding RNAs (ncRNAs) have been found to have roles in a large variety of biological processes. Recent studies indicate that ncRNAs are far more abundant and important than initially imagined, holding great promise for use in diagnostic, prognostic, and therapeutic applications. Within [...] Read more.
Noncoding RNAs (ncRNAs) have been found to have roles in a large variety of biological processes. Recent studies indicate that ncRNAs are far more abundant and important than initially imagined, holding great promise for use in diagnostic, prognostic, and therapeutic applications. Within ncRNAs, microRNAs (miRNAs) are the most widely studied and characterized. They have been implicated in initiation and progression of a variety of human malignancies, including major pathologies such as cancers, arthritis, neurodegenerative disorders, and cardiovascular diseases. Their surprising stability in serum and other bodily fluids led to their rapid ascent as a novel class of biomarkers. For example, several properties of stable miRNAs, and perhaps other classes of ncRNAs, make them good candidate biomarkers for early cancer detection and for determining which preneoplastic lesions are likely to progress to cancer. Of particular interest is the identification of biomarker signatures, which may include traditional protein-based biomarkers, to improve risk assessment, detection, and prognosis. Here, we offer a comprehensive review of the ncRNA biomarker literature and discuss state-of-the-art technologies for their detection. Furthermore, we address the challenges present in miRNA detection and quantification, and outline future perspectives for development of next-generation biodetection assays employing multicolor alternating-laser excitation (ALEX) fluorescence spectroscopy. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
Figures

Open AccessReview ANRIL: Molecular Mechanisms and Implications in Human Health
Int. J. Mol. Sci. 2013, 14(1), 1278-1292; doi:10.3390/ijms14011278
Received: 6 November 2012 / Revised: 28 December 2012 / Accepted: 4 January 2013 / Published: 10 January 2013
Cited by 37 | PDF Full-text (448 KB) | HTML Full-text | XML Full-text
Abstract
ANRIL is a recently discovered long non-coding RNA encoded in the chromosome 9p21 region. This locus is a hotspot for disease-associated polymorphisms, and it has been consistently associated with cardiovascular disease, and more recently with several cancers, diabetes, glaucoma, endometriosis among other [...] Read more.
ANRIL is a recently discovered long non-coding RNA encoded in the chromosome 9p21 region. This locus is a hotspot for disease-associated polymorphisms, and it has been consistently associated with cardiovascular disease, and more recently with several cancers, diabetes, glaucoma, endometriosis among other conditions. ANRIL has been shown to regulate its neighbor tumor suppressors CDKN2A/B by epigenetic mechanisms and thereby regulate cell proliferation and senescence. However, the clear role of ANRIL in the pathogenesis of these conditions is yet to be understood. Here, we review the recent findings on ANRIL molecular characterization and function, with a particular focus on its implications in human disease. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
Open AccessReview Non-Coding RNAs in Retinal Development
Int. J. Mol. Sci. 2012, 13(1), 558-578; doi:10.3390/ijms13010558
Received: 3 December 2011 / Revised: 20 December 2011 / Accepted: 21 December 2011 / Published: 5 January 2012
Cited by 8 | PDF Full-text (371 KB) | HTML Full-text | XML Full-text
Abstract
Retinal development is dependent on an accurately functioning network of transcriptional and translational regulators. Among the diverse classes of molecules involved, non-coding RNAs (ncRNAs) play a significant role. Members of this family are present in the cell as transcripts, but are not [...] Read more.
Retinal development is dependent on an accurately functioning network of transcriptional and translational regulators. Among the diverse classes of molecules involved, non-coding RNAs (ncRNAs) play a significant role. Members of this family are present in the cell as transcripts, but are not translated into proteins. MicroRNAs (miRNAs) are small ncRNAs that act as post-transcriptional regulators. During the last decade, they have been implicated in a variety of biological processes, including the development of the nervous system. On the other hand, long-ncRNAs (lncRNAs) represent a different class of ncRNAs that act mainly through processes involving chromatin remodeling and epigenetic mechanisms. The visual system is a prominent model to investigate the molecular mechanisms underlying neurogenesis or circuit formation and function, including the differentiation of retinal progenitor cells to generate the seven principal cell classes in the retina, pathfinding decisions of retinal ganglion cell axons in order to establish the correct connectivity from the eye to the brain proper, and activity-dependent mechanisms for the functionality of visual circuits. Recent findings have associated ncRNAs in several of these processes and uncovered a new level of complexity for the existing regulatory mechanisms. This review summarizes and highlights the impact of ncRNAs during the development of the vertebrate visual system, with a specific focus on the role of miRNAs and a synopsis regarding recent findings on lncRNAs in the retina. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
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Open AccessReview Non Coding RNAs and Viruses in the Framework of the Phylogeny of the Genes, Epigenesis and Heredity
Int. J. Mol. Sci. 2012, 13(1), 477-490; doi:10.3390/ijms13010477
Received: 23 November 2011 / Revised: 22 December 2011 / Accepted: 23 December 2011 / Published: 4 January 2012
Cited by 4 | PDF Full-text (123 KB) | HTML Full-text | XML Full-text
Abstract
The origin of genes is one of the most enigmatic events in the origin of life. It has been suggested that noncoding (nc) RNA was probably a precursor in the formation of the first polypeptide, and also at the origin of the [...] Read more.
The origin of genes is one of the most enigmatic events in the origin of life. It has been suggested that noncoding (nc) RNA was probably a precursor in the formation of the first polypeptide, and also at the origin of the first manifestation of life and genes. ncRNAs are also becoming central for understanding gene expression and silencing. Indeed, before the discovery of ncRNAs, proteins were viewed as the major molecules in the regulation of gene expression and gene silencing; however, recent findings suggest that ncRNA also plays an important role in gene expression. Reverse transcription of RNA viruses and their integration into the genome of eukaryotes and also their relationship with the ncRNA suggest that their origin is basal in genome evolution, and also probably constitute the first mechanism of gene regulation. I am to review the different roles of ncRNAs in the framework of gene evolution, as well as the importance of ncRNAs and viruses in the epigenesis and in the non-Mendelian model of heredity and evolution. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
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Open AccessReview RNA Aptamer Evolution: Two Decades of SELEction
Int. J. Mol. Sci. 2011, 12(12), 9155-9171; doi:10.3390/ijms12129155
Received: 24 October 2011 / Revised: 24 November 2011 / Accepted: 28 November 2011 / Published: 8 December 2011
Cited by 24 | PDF Full-text (444 KB) | HTML Full-text | XML Full-text
Abstract
Aptamers are small non-coding RNAs capable of recognizing, with high specificity and affinity, a wide variety of molecules in a manner that resembles antibodies. This class of nucleic acids is the resulting product of applying a well-established screening method known as SELEX. [...] Read more.
Aptamers are small non-coding RNAs capable of recognizing, with high specificity and affinity, a wide variety of molecules in a manner that resembles antibodies. This class of nucleic acids is the resulting product of applying a well-established screening method known as SELEX. First developed in 1990, the SELEX process has become a powerful tool to select structured oligonucleotides for the recognition of targets, starting with small molecules, going through protein complexes until whole cells. SELEX has also evolved along with new technologies positioning itself as an alternative in the design of a new class of therapeutic agents in modern molecular medicine. This review is an historical follow-up of SELEX method over the two decades since its first appearance. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
Open AccessReview A Concise Review on Epigenetic Regulation: Insight into Molecular Mechanisms
Int. J. Mol. Sci. 2011, 12(12), 8661-8694; doi:10.3390/ijms12128661
Received: 9 August 2011 / Revised: 7 November 2011 / Accepted: 10 November 2011 / Published: 30 November 2011
Cited by 12 | PDF Full-text (299 KB) | HTML Full-text | XML Full-text
Abstract
Epigenetic mechanisms are responsible for the regulation of transcription of imprinted genes and those that induce a totipotent state. Starting just after fertilization, DNA methylation pattern undergoes establishment, reestablishment and maintenance. These modifications are important for normal embryo and placental developments. Throughout [...] Read more.
Epigenetic mechanisms are responsible for the regulation of transcription of imprinted genes and those that induce a totipotent state. Starting just after fertilization, DNA methylation pattern undergoes establishment, reestablishment and maintenance. These modifications are important for normal embryo and placental developments. Throughout life and passing to the next generation, epigenetic events establish, maintain, erase and reestablish. In the context of differentiated cell reprogramming, demethylation and activation of genes whose expressions contribute to the pluripotent state is the crux of the matter. In this review, firstly, regulatory epigenetic mechanisms related to somatic cell nuclear transfer (SCNT) reprogramming are discussed, followed by embryonic development, and placental epigenetic issues. Full article
(This article belongs to the Special Issue Non-Coding RNAs)
Open AccessReview Identification and Role of Regulatory Non-Coding RNAs in Listeria monocytogenes
Int. J. Mol. Sci. 2011, 12(8), 5070-5079; doi:10.3390/ijms12085070
Received: 28 June 2011 / Revised: 15 July 2011 / Accepted: 8 August 2011 / Published: 10 August 2011
Cited by 9 | PDF Full-text (173 KB) | HTML Full-text | XML Full-text
Abstract
Bacterial regulatory non-coding RNAs control numerous mRNA targets that direct a plethora of biological processes, such as the adaption to environmental changes, growth and virulence. Recently developed high-throughput techniques, such as genomic tiling arrays and RNA-Seq have allowed investigating prokaryotic cis- [...] Read more.
Bacterial regulatory non-coding RNAs control numerous mRNA targets that direct a plethora of biological processes, such as the adaption to environmental changes, growth and virulence. Recently developed high-throughput techniques, such as genomic tiling arrays and RNA-Seq have allowed investigating prokaryotic cis- and trans-acting regulatory RNAs, including sRNAs, asRNAs, untranslated regions (UTR) and riboswitches. As a result, we obtained a more comprehensive view on the complexity and plasticity of the prokaryotic genome biology. Listeria monocytogenes was utilized as a model system for intracellular pathogenic bacteria in several studies, which revealed the presence of about 180 regulatory RNAs in the listerial genome. A regulatory role of non-coding RNAs in survival, virulence and adaptation mechanisms of L. monocytogenes was confirmed in subsequent experiments, thus, providing insight into a multifaceted modulatory function of RNA/mRNA interference. In this review, we discuss the identification of regulatory RNAs by high-throughput techniques and in their functional role in L. monocytogenes. Full article
(This article belongs to the Special Issue Non-Coding RNAs)

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