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Non-coding RNA: 5th Anniversary
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Non-coding RNA: 5th Anniversary

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

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 80178

Special Issue Editor

Prof. Dr. George A. Calin

grade E-Mail Website
Guest Editor
Department of Translational Molecular Pathology, Center for RNA Interference and Non-Coding RNAs, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: non-coding RNA; microRNA; cancer; metastasis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues and Non-coding RNA Aficionados,

It's time to celebrate – the Non-Coding RNA journal is celebrating its 5th anniversary! It is quite an achievement, as the non-coding RNA field is very competitive and the number of journals publishing papers on genes that do not codify for proteins but regulate their roles is increasing each day. This news is good: the journal established its own niche by publishing interesting and well cited papers related to the roles of non-coding RNAs in many organisms and in a plethora of physiologic and disease conditions. Consequently, we are expecting, and curious about, the first impact factor of the journal!

It is time to thank all the members of the Editorial Board who, in spite of their busy schedule, reviewed many papers and contributed scientifically by publishing in the journal. It is also time to thank the authors, as trusting the journal before the impact factor is on the market has risks, but rewards also, if and when the journal keeps growing and establishing an identity, as Non-Coding RNA has done already! And of course, time to thank the editorial staff that kept through dedicated work the journal expanding. And last but not the least, to thank the many passionate readers – without your curiosity and time to read the papers from Non-Coding RNA and without you citing the manuscripts that you enjoyed and trusted, the journal would not exist!

It is also time to prepare a commemorative Special Issue focused on non-coding RNAs. I invite the members of the Editorial Board, the authors of former papers and the readers with passion for ncRNAs to contribute experimental papers or reviews. Any topic that is new and they consider interesting on ncRNAs can be covered! With the editorial staff, I will work on organizing a quick and fair reviewing process to publish the most interesting manuscripts. Science is all about having fun making discoveries and presenting reproducible results that back up creative conclusions!

Thank you all again and keep making discoveries!

Prof. Dr. George A Calin
Guest Editor

Manuscript Submission Information

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. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short 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 thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Non-Coding RNA is an international peer-reviewed open access semimonthly 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 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (18 papers)

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Research

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16 pages, 1713 KiB  
Article
miR-294 and miR-410 Negatively Regulate Tnfa, Arginine Transporter Cat1/2, and Nos2 mRNAs in Murine Macrophages Infected with Leishmania amazonensis
by Stephanie Maia Acuña, Jonathan Miguel Zanatta, Camilla de Almeida Bento, Lucile Maria Floeter-Winter and Sandra Marcia Muxel
Non-Coding RNA 2022, 8(1), 17; https://doi.org/10.3390/ncrna8010017 - 06 Feb 2022
Cited by 5 | Viewed by 2974
Abstract
MicroRNAs are small non-coding RNAs that regulate cellular processes by the post-transcriptional regulation of gene expression, including immune responses. The shift in the miRNA profiling of murine macrophages infected with Leishmania amazonensis can change inflammatory response and metabolism. L-arginine availability and its conversion [...] Read more.
MicroRNAs are small non-coding RNAs that regulate cellular processes by the post-transcriptional regulation of gene expression, including immune responses. The shift in the miRNA profiling of murine macrophages infected with Leishmania amazonensis can change inflammatory response and metabolism. L-arginine availability and its conversion into nitric oxide by nitric oxide synthase 2 (Nos2) or ornithine (a polyamine precursor) by arginase 1/2 regulate macrophage microbicidal activity. This work aimed to evaluate the function of miR-294, miR-301b, and miR-410 during early C57BL/6 bone marrow-derived macrophage infection with L. amazonensis. We observed an upregulation of miR-294 and miR-410 at 4 h of infection, but the levels of miR-301b were not modified. This profile was not observed in LPS-stimulated macrophages. We also observed decreased levels of those miRNAs target genes during infection, such as Cationic amino acid transporters 1 (Cat1/Slc7a1), Cat2/Slc7a22 and Nos2; genes were upregulated in LPS stimuli. The functional inhibition of miR-294 led to the upregulation of Cat2 and Tnfa and the dysregulation of Nos2, while miR-410 increased Cat1 levels. miR-294 inhibition reduced the number of amastigotes per infected macrophage, showing a reduction in the parasite growth inside the macrophage. These data identified miR-294 and miR-410 biomarkers for a potential regulator in the inflammatory profiles of microphages mediated by L. amazonensis infection. This research provides novel insights into immune dysfunction contributing to infection outcomes and suggests the use of the antagomiRs/inhibitors of miR-294 and miR-410 as new therapeutic strategies to modulate inflammation and to decrease parasitism. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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20 pages, 4958 KiB  
Article
Binding of the RNA Chaperone Hfq on Target mRNAs Promotes the Small RNA RyhB-Induced Degradation in Escherichia coli
by David Lalaouna, Karine Prévost, Seongjin Park, Thierry Chénard, Marie-Pier Bouchard, Marie-Pier Caron, Carin K. Vanderpool, Jingyi Fei and Eric Massé
Non-Coding RNA 2021, 7(4), 64; https://doi.org/10.3390/ncrna7040064 - 28 Sep 2021
Cited by 3 | Viewed by 4062
Abstract
Many RNA-RNA interactions depend on molecular chaperones to form and remain stable in living cells. A prime example is the RNA chaperone Hfq, which is a critical effector involved in regulatory interactions between small RNAs (sRNAs) and cognate target mRNAs in Enterobacteriaceae. While [...] Read more.
Many RNA-RNA interactions depend on molecular chaperones to form and remain stable in living cells. A prime example is the RNA chaperone Hfq, which is a critical effector involved in regulatory interactions between small RNAs (sRNAs) and cognate target mRNAs in Enterobacteriaceae. While there is a great deal of in vitro biochemical evidence supporting the model that Hfq enhances rates or affinities of sRNA:mRNA interactions, there is little corroborating in vivo evidence. Here we used in vivo tools including reporter genes, co-purification assays, and super-resolution microscopy to analyze the role of Hfq in RyhB-mediated regulation, and we found that Hfq is often unnecessary for efficient RyhB:mRNA complex formation in vivo. Remarkably, our data suggest that a primary function of Hfq is to promote RyhB-induced cleavage of mRNA targets by RNase E. Moreover, our work indicates that Hfq plays a more limited role in dictating regulatory outcomes following sRNAs RybB and DsrA complex formation with specific target mRNAs. Our investigation helps evaluate the roles played by Hfq in some RNA-mediated regulation. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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27 pages, 6081 KiB  
Article
MicroRNA Isoforms Contribution to Melanoma Pathogenesis
by Elisabetta Broseghini, Emi Dika, Eric Londin and Manuela Ferracin
Non-Coding RNA 2021, 7(4), 63; https://doi.org/10.3390/ncrna7040063 - 27 Sep 2021
Cited by 6 | Viewed by 3590
Abstract
Cutaneous melanoma (CM) is the most lethal tumor among skin cancers, and its incidence is constantly increasing. A deeper understanding of the molecular processes guiding melanoma pathogenesis could improve diagnosis, treatment and prognosis. MicroRNAs play a key role in melanoma biology. Recently, next [...] Read more.
Cutaneous melanoma (CM) is the most lethal tumor among skin cancers, and its incidence is constantly increasing. A deeper understanding of the molecular processes guiding melanoma pathogenesis could improve diagnosis, treatment and prognosis. MicroRNAs play a key role in melanoma biology. Recently, next generation sequencing (NGS) experiments, designed to assess small-RNA expression, revealed the existence of microRNA variants with different length and sequence. These microRNA isoforms are known as isomiRs and provide an additional layer to the complex non-coding RNA world. Here, we collected data from NGS experiments to provide a comprehensive characterization of miRNA and isomiR dysregulation in benign nevi (BN) and early-stage melanomas. We observed that melanoma and BN express different and specific isomiRs and have a different isomiR abundance distribution. Moreover, isomiRs from the same microRNA can have opposite expression trends between groups. Using The Cancer Genome Atlas (TCGA) dataset of skin cancers, we analyzed isomiR expression in primary melanoma and melanoma metastasis and tested their association with NF1, BRAF and NRAS mutations. IsomiRs differentially expressed were identified and catalogued with reference to the canonical form. The reported non-random dysregulation of specific isomiRs contributes to the understanding of the complex melanoma pathogenesis and serves as the basis for further functional studies. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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21 pages, 1784 KiB  
Article
MicroSalmon: A Comprehensive, Searchable Resource of Predicted MicroRNA Targets and 3′UTR Cis-Regulatory Elements in the Full-Length Sequenced Atlantic Salmon Transcriptome
by Sigmund Ramberg and Rune Andreassen
Non-Coding RNA 2021, 7(4), 61; https://doi.org/10.3390/ncrna7040061 - 22 Sep 2021
Cited by 5 | Viewed by 3239
Abstract
Complete 3′UTRs unambiguously assigned to specific mRNA isoforms from the Atlantic salmon full-length (FL) transcriptome were collected into a 3′UTRome. miRNA response elements (MREs) and other cis-regulatory motifs were subsequently predicted and assigned to 3′UTRs of all FL-transcripts. The MicroSalmon GitHub repository provides [...] Read more.
Complete 3′UTRs unambiguously assigned to specific mRNA isoforms from the Atlantic salmon full-length (FL) transcriptome were collected into a 3′UTRome. miRNA response elements (MREs) and other cis-regulatory motifs were subsequently predicted and assigned to 3′UTRs of all FL-transcripts. The MicroSalmon GitHub repository provides all results. RNAHybrid and sRNAtoolbox tools predicted the MREs. UTRscan and the Teiresias algorithm predicted other 3′UTR cis-acting motifs, both known vertebrate motifs and putative novel motifs. MicroSalmon provides search programs to retrieve all FL-transcripts targeted by a miRNA (median number 1487), all miRNAs targeting an FL-transcript (median number 27), and other cis-acting motifs. As thousands of FL-transcripts may be targets of each miRNA, additional experimental strategies are necessary to reduce the likely true and relevant targets to a number that may be functionally validated. Low-complexity motifs known to affect mRNA decay in vertebrates were over-represented. Many of these were enriched in the terminal end, while purine- or pyrimidine-rich motifs with unknown functions were enriched immediately downstream of the stop codon. Furthermore, several novel complex motifs were over-represented, indicating conservation and putative function. In conclusion, MicroSalmon is an extensive and useful, searchable resource for study of Atlantic salmon transcript regulation by miRNAs and cis-acting 3′UTR motifs. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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17 pages, 2519 KiB  
Article
A New Specific and Sensitive RT-qPCR Method Based on Splinted 5′ Ligation for the Quantitative Detection of RNA Species Shorter than microRNAs
by Marine Lambert, Abderrahim Benmoussa and Patrick Provost
Non-Coding RNA 2021, 7(3), 59; https://doi.org/10.3390/ncrna7030059 - 18 Sep 2021
Cited by 3 | Viewed by 4005
Abstract
Recently, we discovered a new family of unusually short RNAs mapping to 5.8S ribosomal RNA (rRNA) and which we named dodecaRNAs (doRNAs), according to the number of core nucleotides (12 nt) their members contain. To confirm these small RNA-sequencing (RNA-Seq) data, validate the [...] Read more.
Recently, we discovered a new family of unusually short RNAs mapping to 5.8S ribosomal RNA (rRNA) and which we named dodecaRNAs (doRNAs), according to the number of core nucleotides (12 nt) their members contain. To confirm these small RNA-sequencing (RNA-Seq) data, validate the existence of the two overly abundant doRNAs—the minimal core 12-nt doRNA sequence and its + 1-nt variant bearing a 5′ Cytosine, C-doRNA—and streamline their analysis, we developed a new specific and sensitive splinted 5′ ligation reverse transcription (RT)-quantitative polymerase chain reaction (qPCR) method. This method is based on a splint-assisted ligation of an adapter to the 5′ end of doRNAs, followed by RT-qPCR amplification and quantitation. Our optimized protocol, which may discriminate between doRNA, C-doRNA, mutated and precursor sequences, can accurately detect as low as 240 copies and is quantitatively linear over a range of 7 logs. This method provides a unique tool to expand and facilitate studies exploring the molecular and cellular biology of RNA species shorter than microRNAs. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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18 pages, 2372 KiB  
Article
Systematic Identification and Functional Validation of New snoRNAs in Human Muscle Progenitors
by Baptiste Bogard, Claire Francastel and Florent Hubé
Non-Coding RNA 2021, 7(3), 56; https://doi.org/10.3390/ncrna7030056 - 13 Sep 2021
Viewed by 2565
Abstract
Small non-coding RNAs (sncRNAs) represent an important class of regulatory RNAs involved in the regulation of transcription, RNA splicing or translation. Among these sncRNAs, small nucleolar RNAs (snoRNAs) mostly originate from intron splicing in humans and are central to posttranscriptional regulation of gene [...] Read more.
Small non-coding RNAs (sncRNAs) represent an important class of regulatory RNAs involved in the regulation of transcription, RNA splicing or translation. Among these sncRNAs, small nucleolar RNAs (snoRNAs) mostly originate from intron splicing in humans and are central to posttranscriptional regulation of gene expression. However, the characterization of the complete repertoire of sncRNAs in a given cellular context and the functional annotation of the human transcriptome are far from complete. Here, we report the large-scale identification of sncRNAs in the size range of 50 to 200 nucleotides without a priori on their biogenesis, structure and genomic origin in the context of normal human muscle cells. We provided a complete set of experimental validation of novel candidate snoRNAs by evaluating the prerequisites for their biogenesis and functionality, leading to their validation as genuine snoRNAs. Interestingly, we also found intergenic snoRNAs, which we showed are in fact integrated into candidate introns of unannotated transcripts or degraded by the Nonsense Mediated Decay pathway. Hence, intergenic snoRNAs represent a new type of landmark for the identification of new transcripts that have gone undetected because of low abundance or degradation after the release of the snoRNA. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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17 pages, 2717 KiB  
Article
17β-Estradiol Regulates miR-9-5p and miR-9-3p Stability and Function in the Aged Female Rat Brain
by Chun K. Kim, Megan L. Linscott, Sarah Flury, Mengjie Zhang, Mikayla L. Newby and Toni R. Pak
Non-Coding RNA 2021, 7(3), 53; https://doi.org/10.3390/ncrna7030053 - 30 Aug 2021
Cited by 4 | Viewed by 2586
Abstract
Clinical studies demonstrated that the ovarian hormone 17β-estradiol (E2) is neuroprotective within a narrow window of time following menopause, suggesting that there is a biological switch in E2 action that is temporally dependent. However, the molecular mechanisms mediating this temporal [...] Read more.
Clinical studies demonstrated that the ovarian hormone 17β-estradiol (E2) is neuroprotective within a narrow window of time following menopause, suggesting that there is a biological switch in E2 action that is temporally dependent. However, the molecular mechanisms mediating this temporal switch have not been determined. Our previous studies focused on microRNAs (miRNA) as one potential molecular mediator and showed that E2 differentially regulated a subset of mature miRNAs which was dependent on age and the length of time following E2 deprivation. Notably, E2 significantly increased both strands of the miR-9 duplex (miR-9-5p and miR-9-3p) in the hypothalamus, raising the possibility that E2 could regulate miRNA stability/degradation. We tested this hypothesis using a biochemical approach to measure miRNA decay in a hypothalamic neuronal cell line and in hypothalamic brain tissue from a rat model of surgical menopause. Notably, we found that E2 treatment stabilized both miRNAs in neuronal cells and in the rat hypothalamus. We also used polysome profiling as a proxy for miR-9-5p and miR-9-3p function and found that E2 was able to shift polysome loading of the miRNAs, which repressed the translation of a predicted miR-9-3p target. Moreover, miR-9-5p and miR-9-3p transcripts appeared to occupy different fractions of the polysome profile, indicating differential subcellular. localization. Together, these studies reveal a novel role for E2 in modulating mature miRNA behavior, independent of its effects at regulating the primary and/or precursor form of miRNAs. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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16 pages, 1777 KiB  
Article
Non-Coding, RNAPII-Dependent Transcription at the Promoters of rRNA Genes Regulates Their Chromatin State in S. cerevisiae
by Emma Lesage, Jorge Perez-Fernandez, Sophie Queille, Christophe Dez, Olivier Gadal and Marta Kwapisz
Non-Coding RNA 2021, 7(3), 41; https://doi.org/10.3390/ncrna7030041 - 11 Jul 2021
Cited by 4 | Viewed by 4276
Abstract
Pervasive transcription is widespread in eukaryotes, generating large families of non-coding RNAs. Such pervasive transcription is a key player in the regulatory pathways controlling chromatin state and gene expression. Here, we describe long non-coding RNAs generated from the ribosomal RNA gene promoter called [...] Read more.
Pervasive transcription is widespread in eukaryotes, generating large families of non-coding RNAs. Such pervasive transcription is a key player in the regulatory pathways controlling chromatin state and gene expression. Here, we describe long non-coding RNAs generated from the ribosomal RNA gene promoter called UPStream-initiating transcripts (UPS). In yeast, rDNA genes are organized in tandem repeats in at least two different chromatin states, either transcribed and largely depleted of nucleosomes (open) or assembled in regular arrays of nucleosomes (closed). The production of UPS transcripts by RNA Polymerase II from endogenous rDNA genes was initially documented in mutants defective for rRNA production by RNA polymerase I. We show here that UPS are produced in wild-type cells from closed rDNA genes but are hidden within the enormous production of rRNA. UPS levels are increased when rDNA chromatin states are modified at high temperatures or entering/leaving quiescence. We discuss their role in the regulation of rDNA chromatin states and rRNA production. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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16 pages, 3941 KiB  
Article
Exosomes in Epilepsy of Tuberous Sclerosis Complex: Carriers of Pro-Inflammatory MicroRNAs
by Daniela Cukovic, Shruti Bagla, Dylan Ukasik, Paul M. Stemmer, Bhanu P. Jena, Akshata R. Naik, Sandeep Sood, Eishi Asano, Aimee Luat, Diane C. Chugani and Alan A. Dombkowski
Non-Coding RNA 2021, 7(3), 40; https://doi.org/10.3390/ncrna7030040 - 10 Jul 2021
Cited by 12 | Viewed by 4459
Abstract
Exosomes are a class of small, secreted extracellular vesicles (EV) that have recently gained considerable attention for their role in normal cellular function, disease processes and potential as biomarkers. Exosomes serve as intercellular messengers and carry molecular cargo that can alter gene expression [...] Read more.
Exosomes are a class of small, secreted extracellular vesicles (EV) that have recently gained considerable attention for their role in normal cellular function, disease processes and potential as biomarkers. Exosomes serve as intercellular messengers and carry molecular cargo that can alter gene expression and the phenotype of recipient cells. Here, we investigated alterations of microRNA cargo in exosomes secreted by epileptogenic tissue in tuberous sclerosis complex (TSC), a multi-system genetic disorder that includes brain lesions known as tubers. Approximately 90% of TSC patients suffer from seizures that originate from tubers, and ~60% are resistant to antiseizure drugs. It is unknown why some tubers cause seizures while others do not, and the molecular basis of drug-resistant epilepsy is not well understood. It is believed that neuroinflammation is involved, and characterization of this mechanism may be key to disrupting the “vicious cycle” between seizures, neuroinflammation, and increased seizure susceptibility. We isolated exosomes from epileptogenic and non-epileptogenic TSC tubers, and we identified differences in their microRNA cargo using small RNA-seq. We identified 12 microRNAs (including miR-142-3p, miR-223-3p and miR-21-5p) that are significantly increased in epileptogenic tubers and contain nucleic acid motifs that activate toll-like receptors (TLR7/8), initiating a neuroinflammatory cascade. Exosomes from epileptogenic tissue caused induction of key pathways in cultured cells, including innate immune signaling (TLR), inflammatory response and key signaling nodes SQSTM1 (p62) and CDKN1A (p21). Genes induced in vitro were also significantly upregulated in epileptogenic tissue. These results provide new evidence on the role of exosomes and non-coding RNA cargo in the neuroinflammatory cascade of epilepsy and may help advance the development of novel biomarkers and therapeutic approaches for the treatment of drug-resistant epilepsy. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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10 pages, 1464 KiB  
Article
miR-24 Targets the Transmembrane Glycoprotein Neuropilin-1 in Human Brain Microvascular Endothelial Cells
by Pasquale Mone, Jessica Gambardella, Xujun Wang, Stanislovas S. Jankauskas, Alessandro Matarese and Gaetano Santulli
Non-Coding RNA 2021, 7(1), 9; https://doi.org/10.3390/ncrna7010009 - 02 Feb 2021
Cited by 45 | Viewed by 5918
Abstract
Neuropilin-1 is a transmembrane glycoprotein that has been implicated in several processes including angiogenesis and immunity. Recent evidence has also shown that it is implied in the cellular internalization of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes the coronavirus disease 2019 [...] Read more.
Neuropilin-1 is a transmembrane glycoprotein that has been implicated in several processes including angiogenesis and immunity. Recent evidence has also shown that it is implied in the cellular internalization of the severe acute respiratory syndrome coronavirus (SARS-CoV-2), which causes the coronavirus disease 2019 (COVID-19). We hypothesized that specific microRNAs can target Neuropilin-1. By combining bioinformatic and functional approaches, we identified miR-24 as a regulator of Neuropilin-1 transcription. Since Neuropilin-1 has been shown to play a key role in the endothelium-mediated regulation of the blood-brain barrier, we validated miR-24 as a functional modulator of Neuropilin-1 in human brain microvascular endothelial cells (hBMECs), which are the most suitable cell line for an in vitro blood–brain barrier model. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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Review

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18 pages, 5648 KiB  
Review
A Structural View of miRNA Biogenesis and Function
by Ana Lúcia Leitão and Francisco J. Enguita
Non-Coding RNA 2022, 8(1), 10; https://doi.org/10.3390/ncrna8010010 - 18 Jan 2022
Cited by 44 | Viewed by 7749
Abstract
Micro-RNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) that act as post-transcriptional regulators of gene expression. Since their discovery in 1993, they have been the subject of deep study due to their involvement in many important biological processes. Compared with other ncRNAs, [...] Read more.
Micro-RNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) that act as post-transcriptional regulators of gene expression. Since their discovery in 1993, they have been the subject of deep study due to their involvement in many important biological processes. Compared with other ncRNAs, miRNAs are generated from devoted transcriptional units which are processed by a specific set of endonucleases. The contribution of structural biology methods for understanding miRNA biogenesis and function has been essential for the dissection of their roles in cell biology and human disease. In this review, we summarize the application of structural biology for the characterization of the molecular players involved in miRNA biogenesis (processors and effectors), starting from the X-ray crystallography methods to the more recent cryo-electron microscopy protocols. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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17 pages, 2069 KiB  
Review
Small RNAs Asserting Big Roles in Mycobacteria
by Fatma S. Coskun, Przemysław Płociński and Nicolai S. C. van Oers
Non-Coding RNA 2021, 7(4), 69; https://doi.org/10.3390/ncrna7040069 - 29 Oct 2021
Cited by 2 | Viewed by 3425
Abstract
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), with 10.4 million new cases per year reported in the human population. Recent studies on the Mtb transcriptome have revealed the abundance of noncoding RNAs expressed at various phases of mycobacteria growth, [...] Read more.
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), with 10.4 million new cases per year reported in the human population. Recent studies on the Mtb transcriptome have revealed the abundance of noncoding RNAs expressed at various phases of mycobacteria growth, in culture, in infected mammalian cells, and in patients. Among these noncoding RNAs are both small RNAs (sRNAs) between 50 and 350 nts in length and smaller RNAs (sncRNA) < 50 nts. In this review, we provide an up-to-date synopsis of the identification, designation, and function of these Mtb-encoded sRNAs and sncRNAs. The methodological advances including RNA sequencing strategies, small RNA antagonists, and locked nucleic acid sequence-specific RNA probes advancing the studies on these small RNA are described. Initial insights into the regulation of the small RNA expression and putative processing enzymes required for their synthesis and function are discussed. There are many open questions remaining about the biological and pathogenic roles of these small non-coding RNAs, and potential research directions needed to define the role of these mycobacterial noncoding RNAs are summarized. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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16 pages, 1632 KiB  
Review
Long Non-Coding RNA Regulation of Epigenetics in Vascular Cells
by Hester Garratt, Robert Ashburn, Miron Sopić, Antonella Nogara, Andrea Caporali and Tijana Mitić
Non-Coding RNA 2021, 7(4), 62; https://doi.org/10.3390/ncrna7040062 - 23 Sep 2021
Cited by 7 | Viewed by 4013
Abstract
The vascular endothelium comprises the interface between the circulation and the vessel wall and, as such, is under the dynamic regulation of vascular signalling, nutrients, and hypoxia. Understanding the molecular drivers behind endothelial cell (EC) and vascular smooth muscle cell (VSMC) function and [...] Read more.
The vascular endothelium comprises the interface between the circulation and the vessel wall and, as such, is under the dynamic regulation of vascular signalling, nutrients, and hypoxia. Understanding the molecular drivers behind endothelial cell (EC) and vascular smooth muscle cell (VSMC) function and dysfunction remains a pivotal task for further clinical progress in tackling vascular disease. A newly emerging era in vascular biology with landmark deep sequencing approaches has provided us with the means to profile diverse layers of transcriptional regulation at a single cell, chromatin, and epigenetic level. This review describes the roles of major vascular long non-coding RNA (lncRNAs) in the epigenetic regulation of EC and VSMC function and discusses the recent progress in their discovery, detection, and functional characterisation. We summarise new findings regarding lncRNA-mediated epigenetic mechanisms—often regulated by hypoxia—within the vascular endothelium and smooth muscle to control vascular homeostasis in health and disease. Furthermore, we outline novel molecular techniques being used in the field to delineate the lncRNA subcellular localisation and interaction with proteins to unravel their biological roles in the epigenetic regulation of vascular genes. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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17 pages, 1536 KiB  
Review
Functional Role of miR-155 in the Pathogenesis of Diabetes Mellitus and Its Complications
by Stanislovas S. Jankauskas, Jessica Gambardella, Celestino Sardu, Angela Lombardi and Gaetano Santulli
Non-Coding RNA 2021, 7(3), 39; https://doi.org/10.3390/ncrna7030039 - 07 Jul 2021
Cited by 40 | Viewed by 5938
Abstract
Substantial evidence indicates that microRNA-155 (miR-155) plays a crucial role in the pathogenesis of diabetes mellitus (DM) and its complications. A number of clinical studies reported low serum levels of miR-155 in patients with type 2 diabetes (T2D). Preclinical studies revealed that miR-155 [...] Read more.
Substantial evidence indicates that microRNA-155 (miR-155) plays a crucial role in the pathogenesis of diabetes mellitus (DM) and its complications. A number of clinical studies reported low serum levels of miR-155 in patients with type 2 diabetes (T2D). Preclinical studies revealed that miR-155 partakes in the phenotypic switch of cells within the islets of Langerhans under metabolic stress. Moreover, miR-155 was shown to regulate insulin sensitivity in liver, adipose tissue, and skeletal muscle. Dysregulation of miR-155 expression was also shown to predict the development of nephropathy, neuropathy, and retinopathy in DM. Here, we systematically describe the reports investigating the role of miR-155 in DM and its complications. We also discuss the recent results from in vivo and in vitro models of type 1 diabetes (T1D) and T2D, discussing the differences between clinical and preclinical studies and shedding light on the molecular pathways mediated by miR-155 in different tissues affected by DM. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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14 pages, 1235 KiB  
Review
Long Non-Coding RNAs in the Control of Gametogenesis: Lessons from Fission Yeast
by Vedrana Andric and Mathieu Rougemaille
Non-Coding RNA 2021, 7(2), 34; https://doi.org/10.3390/ncrna7020034 - 11 Jun 2021
Cited by 7 | Viewed by 4527
Abstract
Long non-coding RNAs (lncRNAs) contribute to cell fate decisions by modulating genome expression and stability. In the fission yeast Schizosaccharomyces pombe, the transition from mitosis to meiosis results in a marked remodeling of gene expression profiles, which ultimately ensures gamete production and [...] Read more.
Long non-coding RNAs (lncRNAs) contribute to cell fate decisions by modulating genome expression and stability. In the fission yeast Schizosaccharomyces pombe, the transition from mitosis to meiosis results in a marked remodeling of gene expression profiles, which ultimately ensures gamete production and inheritance of genetic information to the offspring. This key developmental process involves a set of dedicated lncRNAs that shape cell cycle-dependent transcriptomes through a variety of mechanisms, including epigenetic modifications and the modulation of transcription, post-transcriptional and post-translational regulations, and that contribute to meiosis-specific chromosomal events. In this review, we summarize the biology of these lncRNAs, from their identification to mechanism of action, and discuss their regulatory role in the control of gametogenesis. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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16 pages, 1518 KiB  
Review
Elucidating the Functions of Non-Coding RNAs from the Perspective of RNA Modifications
by Venkata Naga Srikanth Garikipati and Shizuka Uchida
Non-Coding RNA 2021, 7(2), 31; https://doi.org/10.3390/ncrna7020031 - 11 May 2021
Cited by 9 | Viewed by 5170
Abstract
It is now commonly accepted that most of the mammalian genome is transcribed as RNA, yet less than 2% of such RNA encode for proteins. A majority of transcribed RNA exists as non-protein-coding RNAs (ncRNAs) with various functions. Because of the lack of [...] Read more.
It is now commonly accepted that most of the mammalian genome is transcribed as RNA, yet less than 2% of such RNA encode for proteins. A majority of transcribed RNA exists as non-protein-coding RNAs (ncRNAs) with various functions. Because of the lack of sequence homologies among most ncRNAs species, it is difficult to infer the potential functions of ncRNAs by examining sequence patterns, such as catalytic domains, as in the case of proteins. Added to the existing complexity of predicting the functions of the ever-growing number of ncRNAs, increasing evidence suggests that various enzymes modify ncRNAs (e.g., ADARs, METTL3, and METTL14), which has opened up a new field of study called epitranscriptomics. Here, we examine the current status of ncRNA research from the perspective of epitranscriptomics. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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22 pages, 1701 KiB  
Review
Emerging Data on the Diversity of Molecular Mechanisms Involving C/D snoRNAs
by Laeya Baldini, Bruno Charpentier and Stéphane Labialle
Non-Coding RNA 2021, 7(2), 30; https://doi.org/10.3390/ncrna7020030 - 06 May 2021
Cited by 11 | Viewed by 5884
Abstract
Box C/D small nucleolar RNAs (C/D snoRNAs) represent an ancient family of small non-coding RNAs that are classically viewed as housekeeping guides for the 2′-O-methylation of ribosomal RNA in Archaea and Eukaryotes. However, an extensive set of studies now argues that they are [...] Read more.
Box C/D small nucleolar RNAs (C/D snoRNAs) represent an ancient family of small non-coding RNAs that are classically viewed as housekeeping guides for the 2′-O-methylation of ribosomal RNA in Archaea and Eukaryotes. However, an extensive set of studies now argues that they are involved in mechanisms that go well beyond this function. Here, we present these pieces of evidence in light of the current comprehension of the molecular mechanisms that control C/D snoRNA expression and function. From this inventory emerges that an accurate description of these activities at a molecular level is required to let the snoRNA field enter in a second age of maturity. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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18 pages, 1451 KiB  
Review
Non-Coding RNAs in Retinoic Acid as Differentiation and Disease Drivers
by Carlos García-Padilla, Estefanía Lozano-Velasco, Carmen López-Sánchez, Virginio Garcia-Martínez, Amelia Aranega and Diego Franco
Non-Coding RNA 2021, 7(1), 13; https://doi.org/10.3390/ncrna7010013 - 17 Feb 2021
Cited by 3 | Viewed by 4020
Abstract
All-trans retinoic acid (RA) is the most active metabolite of vitamin A. Several studies have described a pivotal role for RA signalling in different biological processes such as cell growth and differentiation, embryonic development and organogenesis. Since RA signalling is highly dose-dependent, a [...] Read more.
All-trans retinoic acid (RA) is the most active metabolite of vitamin A. Several studies have described a pivotal role for RA signalling in different biological processes such as cell growth and differentiation, embryonic development and organogenesis. Since RA signalling is highly dose-dependent, a fine-tuning regulatory mechanism is required. Thus, RA signalling deregulation has a major impact, both in development and disease, related in many cases to oncogenic processes. In this review, we focus on the impact of ncRNA post-transcriptional regulatory mechanisms, especially those of microRNAs and lncRNAs, in RA signalling pathways during differentiation and disease. Full article
(This article belongs to the Special Issue Non-coding RNA: 5th Anniversary)
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