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Regulation by Non-coding RNAs 2022

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 35175

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Prof. Dr. Constantinos Stathopoulos

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Department of Biochemistry, School of Medicine, University of Patras, 26504 Patras, Greece
Interests: protein synthesis inhibitors; antibiotic resistance; novel antibiotics; riboswitch inhibitors; RNA inhibitors
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Dear Colleagues,

During recent years, a remarkable expansion of the “RNA world” members has been observed with the discovery and characterization of many as-yet elusive 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, which cannot be translated into proteins, but also 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 (such as the 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 have 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

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Keywords

regulatory RNA
sRNA
ncRNA
lncRNA
miRNA
siRNA
piRNA
CRISPR RNA
regulatory small RNA fragments

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Regulation by non-coding RNAs 2013 in International Journal of Molecular Sciences (52 articles)

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Research

Jump to: Review

12 pages, 2350 KiB

Open AccessArticle

The Second Class of Tetrahydrofolate (THF-II) Riboswitches Recognizes the Tetrahydrofolic Acid Ligand via Local Conformation Changes

by Minmin Zhang, Guangfeng Liu, Yunlong Zhang, Ting Chen, Shanshan Feng, Rujie Cai and Changrui Lu

Int. J. Mol. Sci. 2022, 23(11), 5903; https://doi.org/10.3390/ijms23115903 - 25 May 2022

Cited by 6 | Viewed by 2200

Abstract

Riboswitches are regulatory noncoding RNAs found in bacteria, fungi and plants, that modulate gene expressions through structural changes in response to ligand binding. Understanding how ligands interact with riboswitches in solution can shed light on the molecular mechanisms of this ancient regulators. Previous studies showed that riboswitches undergo global conformation changes in response to ligand binding to relay information. Here, we report conformation switching models of the recently discovered tetrahydrofolic acid-responsive second class of tetrahydrofolate (THF-II) riboswitches in response to ligand binding. Using a combination of selective 2′-hydroxyl acylation, analyzed by primer extension (SHAPE) assay, 3D modeling and small-angle X-ray scattering (SAXS), we found that the ligand specifically recognizes and reshapes the THF-II riboswitch loop regions, but does not affect the stability of the P3 helix. Our results show that the THF-II riboswitch undergoes only local conformation changes in response to ligand binding, rearranging the Loop1-P3-Loop2 region and rotating Loop1 from a ~120° angle to a ~75° angle. This distinct conformation changes suggest a unique regulatory mechanism of the THF-II riboswitch, previously unseen in other riboswitches. Our findings may contribute to the fields of RNA sensors and drug design. Full article

(This article belongs to the Special Issue Regulation by Non-coding RNAs 2022)

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18 pages, 4919 KiB

Open AccessArticle

Cryo-Treatment Enhances the Embryogenicity of Mature Somatic Embryos via the lncRNA–miRNA–mRNA Network in White Spruce

by Ying Gao, Ying Cui, Ruirui Zhao, Xiaoyi Chen, Jinfeng Zhang, Jian Zhao and Lisheng Kong

Int. J. Mol. Sci. 2022, 23(3), 1111; https://doi.org/10.3390/ijms23031111 - 20 Jan 2022

Cited by 19 | Viewed by 2866

Abstract

In conifers, somatic embryogenesis is uniquely initiated from immature embryos in a narrow time window, which is considerably hindered by the difficulty to induce embryogenic tissue (ET) from other tissues, including mature somatic embryos. In this study, the embryogenic ability of newly induced ET and DNA methylation levels was detected, and whole-transcriptome sequencing analyses were carried out. The results showed that ultra-low temperature treatment significantly enhanced ET induction from mature somatic embryos, with the induction rate from 0.4% to 15.5%, but the underlying mechanisms remain unclear. The newly induced ET showed higher capability in generating mature embryos than the original ET. DNA methylation levels fluctuated during the ET induction process. Here, WGCNA analysis revealed that OPT4, TIP1-1, Chi I, GASA5, GST, LAX3, WRKY7, MYBS3, LRR-RLK, PBL7, and WIN1 genes are involved in stress response and auxin signal transduction. Through co-expression analysis, lncRNAs MSTRG.505746.1, MSTRG.1070680.1, and MSTRG.33602.1 might bind to pre-novel_miR_339 to promote the expression of WRKY7 genes for stress response; LAX3 could be protected by lncRNAs MSTRG.1070680.1 and MSTRG.33602.1 via serving as sponges for novel_miR_495 to initiate auxin signal transduction; lncRNAs MSTRG.505746.1, MSTRG.1070680.1, and MSTRG.33602.1 might serve as sponges for novel_miR_527 to enhance the expression of Chi I for early somatic embryo development. This study provides new insight into the area of stress-enhanced early somatic embryogenesis in conifers, which is also attributable to practical applications. Full article

(This article belongs to the Special Issue Regulation by Non-coding RNAs 2022)

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Review

Jump to: Research

13 pages, 2147 KiB

Open AccessReview

The Intersection of Non-Coding RNAs Contributes to Forest Trees’ Response to Abiotic Stress

by Dandan Xiao, Min Chen, Xiaoqian Yang, Hai Bao, Yuzhang Yang and Yanwei Wang

Int. J. Mol. Sci. 2022, 23(12), 6365; https://doi.org/10.3390/ijms23126365 - 7 Jun 2022

Cited by 6 | Viewed by 1981

Abstract

Non-coding RNAs (ncRNAs) play essential roles in plants by modulating the expression of genes at the transcriptional or post-transcriptional level. In recent years, ncRNAs have been recognized as crucial regulators for growth and development in forest trees, and ncRNAs that respond to various abiotic stresses are now under intense study. In this review, we summarized recent advances in the understanding of abiotic stress-responsive microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in forest trees. Furthermore, we analyzed the intersection of miRNAs, and epigenetic modified ncRNAs of forest trees in response to abiotic stress. In particular, the abiotic stress-related lncRNA/circRNA–miRNA–mRNA regulatory network of forest trees was explored. Full article

(This article belongs to the Special Issue Regulation by Non-coding RNAs 2022)

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26 pages, 779 KiB

Open AccessReview

The Emerging Roles of Long Non-Coding RNAs in Intellectual Disability and Related Neurodevelopmental Disorders

by Carla Liaci, Lucia Prandi, Lisa Pavinato, Alfredo Brusco, Mara Maldotti, Ivan Molineris, Salvatore Oliviero and Giorgio R. Merlo

Int. J. Mol. Sci. 2022, 23(11), 6118; https://doi.org/10.3390/ijms23116118 - 30 May 2022

Cited by 3 | Viewed by 2969

Abstract

In the human brain, long non-coding RNAs (lncRNAs) are widely expressed in an exquisitely temporally and spatially regulated manner, thus suggesting their contribution to normal brain development and their probable involvement in the molecular pathology of neurodevelopmental disorders (NDD). Bypassing the classic protein-centric conception of disease mechanisms, some studies have been conducted to identify and characterize the putative roles of non-coding sequences in the genetic pathogenesis and diagnosis of complex diseases. However, their involvement in NDD, and more specifically in intellectual disability (ID), is still poorly documented and only a few genomic alterations affecting the lncRNAs function and/or expression have been causally linked to the disease endophenotype. Considering that a significant fraction of patients still lacks a genetic or molecular explanation, we expect that a deeper investigation of the non-coding genome will unravel novel pathogenic mechanisms, opening new translational opportunities. Here, we present evidence of the possible involvement of many lncRNAs in the etiology of different forms of ID and NDD, grouping the candidate disease-genes in the most frequently affected cellular processes in which ID-risk genes were previously collected. We also illustrate new approaches for the identification and prioritization of NDD-risk lncRNAs, together with the current strategies to exploit them in diagnosis. Full article

(This article belongs to the Special Issue Regulation by Non-coding RNAs 2022)

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16 pages, 1338 KiB

Open AccessReview

Compartment-Specific Proximity Ligation Expands the Toolbox to Assess the Interactome of the Long Non-Coding RNA NEAT1

by Victoria Mamontova, Barbara Trifault and Kaspar Burger

Int. J. Mol. Sci. 2022, 23(8), 4432; https://doi.org/10.3390/ijms23084432 - 17 Apr 2022

Cited by 4 | Viewed by 3349

Abstract

The nuclear paraspeckle assembly transcript 1 (NEAT1) locus encodes two long non-coding (lnc)RNA isoforms that are upregulated in many tumours and dynamically expressed in response to stress. NEAT1 transcripts form ribonucleoprotein complexes with numerous RNA-binding proteins (RBPs) to assemble paraspeckles and modulate the localisation and activity of gene regulatory enzymes as well as a subset of messenger (m)RNA transcripts. The investigation of the dynamic composition of NEAT1-associated proteins and mRNAs is critical to understand the function of NEAT1. Interestingly, a growing number of biochemical and genetic tools to assess NEAT1 interactomes has been reported. Here, we discuss the Hybridisation Proximity (HyPro) labeling technique in the context of NEAT1. HyPro labeling is a recently developed method to detect spatially ordered interactions of RNA-containing nuclear compartments in cultured human cells. After introducing NEAT1 and paraspeckles, we describe the advantages of the HyPro technology in the context of other methods to study RNA interactomes, and review the key findings in mapping NEAT1-associated RNA transcripts and protein binding partners. We further discuss the limitations and potential improvements of HyPro labeling, and conclude by delineating its applicability in paraspeckles-related cancer research. Full article

(This article belongs to the Special Issue Regulation by Non-coding RNAs 2022)

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23 pages, 1072 KiB

Open AccessReview

Current Advances in RNA Therapeutics for Human Diseases

by Hannah Zogg, Rajan Singh and Seungil Ro

Int. J. Mol. Sci. 2022, 23(5), 2736; https://doi.org/10.3390/ijms23052736 - 1 Mar 2022

Cited by 98 | Viewed by 9264

Abstract

Following the discovery of nucleic acids by Friedrich Miescher in 1868, DNA and RNA were recognized as the genetic code containing the necessary information for proper cell functioning. In the years following these discoveries, vast knowledge of the seemingly endless roles of RNA have become better understood. Additionally, many new types of RNAs were discovered that seemed to have no coding properties (non-coding RNAs), such as microRNAs (miRNAs). The discovery of these new RNAs created a new avenue for treating various human diseases. However, RNA is relatively unstable and is degraded fairly rapidly once administered; this has led to the development of novel delivery mechanisms, such as nanoparticles to increase stability as well as to prevent off-target effects of these molecules. Current advances in RNA-based therapies have substantial promise in treating and preventing many human diseases and disorders through fixing the pathology instead of merely treating the symptomology similarly to traditional therapeutics. Although many RNA therapeutics have made it to clinical trials, only a few have been FDA approved thus far. Additionally, the results of clinical trials for RNA therapeutics have been ambivalent to date, with some studies demonstrating potent efficacy, whereas others have limited effectiveness and/or toxicity. Momentum is building in the clinic for RNA therapeutics; future clinical care of human diseases will likely comprise promising RNA therapeutics. This review focuses on the current advances of RNA therapeutics and addresses current challenges with their development. Full article

(This article belongs to the Special Issue Regulation by Non-coding RNAs 2022)

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16 pages, 890 KiB

Open AccessReview

The Emerging Role of Non-Coding RNAs in the Regulation of Virus Replication and Resultant Cellular Pathologies

by Soudeh Ghafouri-Fard, Bashdar Mahmud Hussen, Hazha Hadayat Jamal, Mohammad Taheri and Guive Sharifi

Int. J. Mol. Sci. 2022, 23(2), 815; https://doi.org/10.3390/ijms23020815 - 13 Jan 2022

Cited by 4 | Viewed by 2839

Abstract

Non-coding RNAs, particularly lncRNAs and miRNAs, have recently been shown to regulate different steps in viral infections and induction of immune responses against viruses. Expressions of several host and viral lncRNAs have been found to be altered during viral infection. These lncRNAs can exert antiviral function via inhibition of viral infection or stimulation of antiviral immune response. Some other lncRNAs can promote viral replication or suppress antiviral responses. The current review summarizes the interaction between ncRNAs and herpes simplex virus, cytomegalovirus, and Epstein–Barr infections. The data presented in this review helps identify viral-related regulators and proposes novel strategies for the prevention and treatment of viral infection. Full article

(This article belongs to the Special Issue Regulation by Non-coding RNAs 2022)

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18 pages, 1500 KiB

Open AccessReview

A Review on the Role of miR-149-5p in the Carcinogenesis

by Soudeh Ghafouri-Fard, Tayyebeh Khoshbakht, Bashdar Mahmud Hussen, Sepideh Kadkhoda, Mohammad Taheri and Arash Tafrishinejad

Int. J. Mol. Sci. 2022, 23(1), 415; https://doi.org/10.3390/ijms23010415 - 30 Dec 2021

Cited by 15 | Viewed by 2458

Abstract

miR-149 is an miRNA with essential roles in carcinogenesis. This miRNA is encoded by the MIR149 gene on 2q37.3. The miR-149 hairpin produces miR-149-5p and miR-149-3p, which are the “guide” and the sister “passenger” strands, respectively. Deep sequencing experiments have shown higher prevalence of miR-149-5p compared with miR-149-3p. Notably, both oncogenic and tumor suppressive roles have been reported for miR-149-5p. In this review, we summarize the impact of miR-149-5p in the tumorigenesis and elaborate mechanisms of its involvement in this process in a variety of neoplastic conditions based on three lines of evidence, i.e., in vitro, in vivo and clinical settings. Full article

(This article belongs to the Special Issue Regulation by Non-coding RNAs 2022)

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15 pages, 275 KiB

Open AccessReview

A Review on the Role of Non-Coding RNAs in the Pathogenesis of Myasthenia Gravis

by Soudeh Ghafouri-Fard, Tahereh Azimi, Bashdar Mahmud Hussen, Mohammad Taheri and Reza Jalili Khoshnoud

Int. J. Mol. Sci. 2021, 22(23), 12964; https://doi.org/10.3390/ijms222312964 - 30 Nov 2021

Cited by 12 | Viewed by 2628

Abstract

Myasthenia gravis (MG) is an autoimmune condition related to autoantibodies against certain proteins in the postsynaptic membranes in the neuromuscular junction. This disorder has a multifactorial inheritance. The connection between environmental and genetic factors can be established by epigenetic factors, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). XLOC_003810, SNHG16, IFNG-AS1, and MALAT-1 are among the lncRNAs with a possible role in the pathoetiology of MG. Moreover, miR-150-5p, miR-155, miR-146a-5p, miR-20b, miR-21-5p, miR-126, let-7a-5p, and let-7f-5p are among miRNAs whose roles in the pathogenesis of MG has been assessed. In the current review, we summarize the impact of miRNAs and lncRNAs in the development or progression of MG. Full article

(This article belongs to the Special Issue Regulation by Non-coding RNAs 2022)

20 pages, 8599 KiB

Open AccessReview

The Dynamic Network of RNP RNase P Subunits

by Athanasios-Nasir Shaukat, Eleni G. Kaliatsi, Ilias Skeparnias and Constantinos Stathopoulos

Int. J. Mol. Sci. 2021, 22(19), 10307; https://doi.org/10.3390/ijms221910307 - 24 Sep 2021

Cited by 8 | Viewed by 3264

Abstract

Ribonuclease P (RNase P) is an important ribonucleoprotein (RNP), responsible for the maturation of the 5′ end of precursor tRNAs (pre-tRNAs). In all organisms, the cleavage activity of a single phosphodiester bond adjacent to the first nucleotide of the acceptor stem is indispensable for cell viability and lies within an essential catalytic RNA subunit. Although RNase P is a ribozyme, its kinetic efficiency in vivo, as well as its structural variability and complexity throughout evolution, requires the presence of one protein subunit in bacteria to several protein partners in archaea and eukaryotes. Moreover, the existence of protein-only RNase P (PRORP) enzymes in several organisms and organelles suggests a more complex evolutionary timeline than previously thought. Recent detailed structures of bacterial, archaeal, human and mitochondrial RNase P complexes suggest that, although apparently dissimilar enzymes, they all recognize pre-tRNAs through conserved interactions. Interestingly, individual protein subunits of the human nuclear and mitochondrial holoenzymes have additional functions and contribute to a dynamic network of elaborate interactions and cellular processes. Herein, we summarize the role of each RNase P subunit with a focus on the human nuclear RNP and its putative role in flawless gene expression in light of recent structural studies. Full article

(This article belongs to the Special Issue Regulation by Non-coding RNAs 2022)

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