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ncRNA
Volume 1
Issue 3
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Non-Coding RNA, Volume 1, Issue 3 (December 2015) – 6 articles , Pages 170-288

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632 KiB  
Editorial
The Non-Coding RNA Journal Club: Highlights on Recent Papers—3
by Ioana Berindan-Neagoe, George Adrian Calin, Claire Francastel, Florent Hubé and Gaetano Santulli
Non-Coding RNA 2015, 1(3), 285-288; https://doi.org/10.3390/ncrna1030285 - 21 Dec 2015
Cited by 1 | Viewed by 4265
Abstract
We are glad to share with you our third Journal Club and to highlight some of the most interesting papers published recently. [...] Full article
(This article belongs to the Collection The Non-Coding RNA Journal Club: Highlights on Recent Papers)
1035 KiB  
Article
Truncated Isoforms of lncRNA ANRIL Are Overexpressed in Bladder Cancer, But Do Not Contribute to Repression of INK4 Tumor Suppressors
by Michèle J. Hoffmann, Judith Dehn, Johanna Droop, Günter Niegisch, Christian Niedworok, Tibor Szarvas and Wolfgang A. Schulz
Non-Coding RNA 2015, 1(3), 266-284; https://doi.org/10.3390/ncrna1030266 - 17 Dec 2015
Cited by 22 | Viewed by 6203
Abstract
The INK4/ARF locus at chromosome 9p21 encoding p14ARF, p15INK4B and p16INK4A is a major tumor suppressor locus, constituting an important barrier for tumor growth. It is frequently inactivated in cancers, especially in urothelial carcinoma (UC). In addition [...] Read more.
The INK4/ARF locus at chromosome 9p21 encoding p14ARF, p15INK4B and p16INK4A is a major tumor suppressor locus, constituting an important barrier for tumor growth. It is frequently inactivated in cancers, especially in urothelial carcinoma (UC). In addition to deletions and DNA hypermethylation, further epigenetic mechanisms might underlie its repression. One candidate factor is the long noncoding RNA ANRIL, which recruits Polycomb proteins (PcG) to regulate expression of target genes in cis and trans. We observed ANRIL overexpression in many UC tissues and cell lines mainly resulting from upregulation of 3’-truncated isoforms. However, aberrant ANRIL expression was neither associated with repression of INK4/ARF genes nor with proliferation activity or senescence. We wondered whether truncated ANRIL isoforms exhibit altered properties resulting in loss of function in cis. We excluded delocalization and performed RNA immunoprecipitation demonstrating interaction between full length or truncated ANRIL and PcG protein CBX7, but not SUZ12 of PRC2. Our data indicate that ANRIL in UC cells may not interact with PRC2, which is central for initializing gene repression. Thus, tissue-specific binding activities between ANRIL and PcG proteins may determine the regulatory function of ANRIL. In conclusion, ANRIL does not play a major role in repression of the INK4/ARF locus in UC. Full article
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1019 KiB  
Article
Antisense Activity across the Nesp Promoter is Required for Nespas-Mediated Silencing in the Imprinted Gnas Cluster
by Charlotte J. Tibbit, Christine M. Williamson, Stuti Mehta, Simon T. Ball, Mita Chotalia, Wade T. Nottingham, Sally A. Eaton, Mohamed M. Quwailid, Lydia Teboul, Gavin Kelsey and Jo Peters
Non-Coding RNA 2015, 1(3), 246-265; https://doi.org/10.3390/ncrna1030246 - 30 Nov 2015
Cited by 10 | Viewed by 5458
Abstract
Macro long non-coding RNAs (lncRNAs) play major roles in gene silencing in inprinted gene clusters. Within the imprinted Gnas cluster, the paternally expressed Nespas lncRNA downregulates its sense counterpart Nesp. To explore the mechanism of action of Nespas, we generated two [...] Read more.
Macro long non-coding RNAs (lncRNAs) play major roles in gene silencing in inprinted gene clusters. Within the imprinted Gnas cluster, the paternally expressed Nespas lncRNA downregulates its sense counterpart Nesp. To explore the mechanism of action of Nespas, we generated two new knock-in alleles to truncate Nespas upstream and downstream of the Nesp promoter. We show that Nespas is essential for methylation of the Nesp differentially methylated region (DMR), but higher levels of Nespas are required for methylation than are needed for downregulation of Nesp. Although Nespas is transcribed for over 27 kb, only Nespas transcript/transcription across a 2.6 kb region that includes the Nesp promoter is necessary for methylation of the Nesp DMR. In both mutants, the levels of Nespas were extraordinarily high, due at least in part to increased stability, an effect not seen with other imprinted lncRNAs. However, even when levels were greatly raised, Nespas remained exclusively cis-acting. We propose Nespas regulates Nesp methylation and expression to ensure appropriate levels of expression of the protein coding transcripts Gnasxl and Gnas on the paternal chromosome. Thus, Nespas mediates paternal gene expression over the entire Gnas cluster via a single gene, Nesp. Full article
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1171 KiB  
Article
miRNA–mRNA Conflux Regulating Immunity and Oxidative Stress Pathways in the Midgut of Blood-Fed Anopheles stephensi
by Shanu Jain, Jatin Shrinet, Adak Tridibes, Raj K. Bhatnagar and Sujatha Sunil
Non-Coding RNA 2015, 1(3), 222-245; https://doi.org/10.3390/ncrna1030222 - 19 Nov 2015
Cited by 4 | Viewed by 6239
Abstract
Blood feeding in Anopheles stephensi initiates a cascade of events that modulate several physiological functions in the mosquito. The midgut epithelium activates several of its molecules, most important among these being microRNAs, which regulate some of the physiological changes by targeting diverse mRNAs. [...] Read more.
Blood feeding in Anopheles stephensi initiates a cascade of events that modulate several physiological functions in the mosquito. The midgut epithelium activates several of its molecules, most important among these being microRNAs, which regulate some of the physiological changes by targeting diverse mRNAs. The present study was conducted to identify and evaluate interactions between targets of eight miRNAs that are regulated on blood feeding. Identified from our previous study, we show these eight miRNAs exhibited distinct tissue specific expression. Targets of these miRNAs were predicted using computational approaches involving bioinformatics, co-expression analysis of the transcriptome and miRNome of blood-fed An. stephensi midgut. Using degradome sequencing, we identified some cleaved mRNAs of these microRNAs and, by using antagomiR knockdown technology to repress the miRNAs, the targets were validated in an An. stephensi cell line and in An. stephensi mosquitoes. In-depth analysis of predicted and identified targets revealed that the regulated miRNAs modulate well-characterized molecules that are involved in combating oxidative stress and immunity pathways through a dynamic miRNA:mRNA network. Our study is the first to identify miRNA:mRNA interactomes that play important role in maintaining redox homeostasis during blood feeding in the midgut of An. stephensi. Full article
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805 KiB  
Review
The Role of MicroRNAs in Kidney Disease
by Sydwell Mukhadi, Rodney Hull, Zukile Mbita and Zodwa Dlamini
Non-Coding RNA 2015, 1(3), 192-221; https://doi.org/10.3390/ncrna1030192 - 18 Nov 2015
Cited by 23 | Viewed by 9410
Abstract
MicroRNAs (miRNAs) are short noncoding RNAs that regulate pathophysiological processes that suppress gene expression by binding to messenger RNAs. These biomolecules can be used to study gene regulation and protein expression, which will allow better understanding of many biological processes such as cell [...] Read more.
MicroRNAs (miRNAs) are short noncoding RNAs that regulate pathophysiological processes that suppress gene expression by binding to messenger RNAs. These biomolecules can be used to study gene regulation and protein expression, which will allow better understanding of many biological processes such as cell cycle progression and apoptosis that control the fate of cells. Several pathways have also been implicated to be involved in kidney diseases such as Transforming Growth Factor-β, Mitogen-Activated Protein Kinase signaling, and Wnt signaling pathways. The discovery of miRNAs has provided new insights into kidney pathologies and may provide new innovative and effective therapeutic strategies. Research has demonstrated the role of miRNAs in a variety of kidney diseases including renal cell carcinoma, diabetic nephropathy, nephritic syndrome, renal fibrosis, lupus nephritis and acute pyelonephritis. MiRNAs are implicated as playing a role in these diseases due to their role in apoptosis, cell proliferation, differentiation and development. As miRNAs have been detected in a stable condition in different biological fluids, they have the potential to be tools to study the pathogenesis of human diseases with a great potential to be used in disease prognosis and diagnosis. The purpose of this review is to examine the role of miRNA in kidney disease. Full article
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658 KiB  
Article
Epstein-Barr Virus EBER Transcripts Affect miRNA-Mediated Regulation of Specific Targets and Are Processed to Small RNA Species
by Julia Alles, Daniele Hasler, Syed Mohammad Ali Kazmi, Mathias Tesson, Andrew Hamilton, Linda Schlegel, Stefanie Marx, Norbert Eichner, Richard Reinhardt, Gunter Meister, Joanna B. Wilson and Friedrich A. Grässer
Non-Coding RNA 2015, 1(3), 170-191; https://doi.org/10.3390/ncrna1030170 - 30 Sep 2015
Cited by 7 | Viewed by 7267
Abstract
The oncogenic Epstein-Barr virus (EBV) expresses 44 mature microRNAs and two non-coding EBER RNAs of 167 (EBER1) and 172 (EBER2) nt length. MiRNA profiling of NK/T cell lines and primary cells and Northern blotting of EBV-infected cell lines and primary tumors revealed processing [...] Read more.
The oncogenic Epstein-Barr virus (EBV) expresses 44 mature microRNAs and two non-coding EBER RNAs of 167 (EBER1) and 172 (EBER2) nt length. MiRNA profiling of NK/T cell lines and primary cells and Northern blotting of EBV-infected cell lines and primary tumors revealed processing of EBER1 to short 5′-derived RNAs of approximately 23, 52 and 70 nt (EBER123, EBER152, and EBER170) and of EBER2 to 3′ fragments. The biogenesis of these species is independent of Dicer, and EBER123 does not act like a miRNA OPEN ACCESS Non-Coding RNA 2015, 1 171 to target its complementary sequence. EBER1, EBER2 and EBER123 were bound by the lupus antigen (La), a nuclear and cytoplasmic protein that facilitates RNAi. Consistent with this, the EBERs affect regulation of interleukin 1alpha (IL1α) and RAC1 reporters harboring miR target sequences, targets of miR-142-3p. However, the EBERs have no effect upon another target of miR-142-3p, ADCY9, nor on TOMM22, a target of ebv-miR-BART16, indicative of selective modulation of gene expression by the EBERs. Full article
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