scholarly journals Biological relevance and therapeutic potential of G-quadruplex structures in the human noncoding transcriptome

2021 ◽  
Vol 49 (7) ◽  
pp. 3617-3633
Author(s):  
Martina Tassinari ◽  
Sara N Richter ◽  
Paolo Gandellini
Keyword(s):  
Gene Expression ◽  
Protein Interactions ◽  
Noncoding Rna ◽  
Therapeutic Potential ◽  
Functional Characterization ◽  
Noncoding Rnas ◽  
Tertiary Structures ◽  
Form Complex ◽  
G Quadruplex ◽  
Rna Interaction

Abstract Noncoding RNAs are functional transcripts that are not translated into proteins. They represent the largest portion of the human transcriptome and have been shown to regulate gene expression networks in both physiological and pathological cell conditions. Research in this field has made remarkable progress in the comprehension of how aberrations in noncoding RNA drive relevant disease-associated phenotypes; however, the biological role and mechanism of action of several noncoding RNAs still need full understanding. Besides fulfilling its function through sequence-based mechanisms, RNA can form complex secondary and tertiary structures which allow non-canonical interactions with proteins and/or other nucleic acids. In this context, the presence of G-quadruplexes in microRNAs and long noncoding RNAs is increasingly being reported. This evidence suggests a role for RNA G-quadruplexes in controlling microRNA biogenesis and mediating noncoding RNA interaction with biological partners, thus ultimately regulating gene expression. Here, we review the state of the art of G-quadruplexes in the noncoding transcriptome, with their structural and functional characterization. In light of the existence and further possible development of G-quadruplex binders that modulate G-quadruplex conformation and protein interactions, we also discuss the therapeutic potential of G-quadruplexes as targets to interfere with disease-associated noncoding RNAs.

scholarly journals Long Noncoding RNA: Regulatory Mechanisms and Therapeutic Potential in Sepsis

2021 ◽  
Vol 11 ◽  
Author(s):  
Wei Wang ◽  
Ni Yang ◽  
Ri Wen ◽  
Chun-Feng Liu ◽  
Tie-Ning Zhang
Keyword(s):  
Host Response ◽  
Noncoding Rna ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Specific Treatment ◽  
Kidney Injury ◽  
Biological Processes ◽  
Immune Functions ◽  
Life Threatening ◽  
Organ Dysfunctions

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and is characterized by a hyperinflammatory state accompanied by immunosuppression. Long noncoding RNAs (lncRNAs) are noncoding RNAs longer than 200 nucleotides and have important roles in mediating various biological processes. Recently, lncRNAs were found to exert both promotive and inhibitory immune functions in sepsis, thus participating in sepsis regulation. Additionally, several studies have revealed that lncRNAs are involved in sepsis-induced organ dysfunctions, including cardiovascular dysfunction, acute lung injury, and acute kidney injury. Considering the lack of effective biomarkers for early identification and specific treatment for sepsis, lncRNAs may be promising biomarkers and even targets for sepsis therapies. This review systematically highlights the recent advances regarding the roles of lncRNAs in sepsis and sheds light on their use as potential biomarkers and treatment targets for sepsis.

scholarly journals Long Noncoding RNA Plays a Key Role in Metastasis and Prognosis of Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Guangbing Li ◽  
Haohai Zhang ◽  
Xueshuai Wan ◽  
Xiaobo Yang ◽  
Chengpei Zhu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Regulation Of Gene Expression ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Comprehensive Review ◽  
Cellular Processes

Long noncoding RNAs (lncRNAs) have been attracting immense research interests. However, only a handful of lncRNAs had been thoroughly characterized. They were involved in fundamental cellular processes including regulation of gene expression at epigenetics as well as tumorogenesis. In this paper, we give a systematic and comprehensive review of existing literature about lncRNA involvement in hepatocellular carcinoma. This review exhibited that lncRNAs played important roles in tumorigenesis and subsequent prognosis and metastasis of hepatocellular carcinoma and elucidated the role of some specific lncRNAs such as MALAT1 and HOTAIR in the pathophysiology of hepatocellular carcinoma and their potential of being therapeutic targets.

scholarly journals Enzymatic RNA Biotinylation for Affinity Purification and Identification of RNA-protein Interactions

2020 ◽  
Author(s):  
Kayla N. Busby ◽  
Amitkumar Fulzele ◽  
Dongyang Zhang ◽  
Eric J. Bennett ◽  
Neal K. Devaraj
Keyword(s):  
Protein Interactions ◽  
Mammalian Cells ◽  
Noncoding Rna ◽  
Affinity Purification ◽  
Functional Characterization ◽  
Selective Enrichment ◽  
Binding Partners ◽  
Nucleotide Mutation ◽  
Rna Biology ◽  
And Function

ABSTRACTThroughout their cellular lifetime, RNA transcripts are bound to proteins, playing crucial roles in RNA metabolism, trafficking, and function. Despite the importance of these interactions, identifying the proteins that interact with an RNA of interest in mammalian cells represents a major challenge in RNA biology. Leveraging the ability to site-specifically and covalently label an RNA of interest using E. Coli tRNA guanine transglycosylase and an unnatural nucleobase substrate, we establish the identification of RNA-protein interactions and the selective enrichment of cellular RNA in mammalian systems. We demonstrate the utility of this approach through the identification of known binding partners of 7SK snRNA via mass spectrometry. Through a minimal 4-nucleotide mutation of the long noncoding RNA HOTAIR, enzymatic biotinylation enables identification putative HOTAIR binding partners in MCF7 breast cancer cells that suggest new potential pathways for oncogenic function. Furthermore, using RNA sequencing and qPCR, we establish that an engineered enzyme variant achieves high levels of labeling selectivity against the human transcriptome allowing for 145-fold enrichment of cellular RNA directly from mammalian cell lysates. The flexibility and breadth of this approach suggests that this system could be routinely applied to the functional characterization of RNA, greatly expanding the toolbox available for studying mammalian RNA biology.

scholarly journals Focus on Noncoding RNA Regulation of Plant-Microbe Interactions

2016 ◽  
Vol 29 (3) ◽  
pp. 155-155
Author(s):  
John P. Carr ◽  
Steven A. Whitham
Keyword(s):  
Gene Expression ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Rna Regulation ◽  
Rna Molecules ◽  
Microbial Origin ◽  
Microbe Interactions ◽  
Satellite Rnas

Investigations in recent years have uncovered important roles for RNA molecules that do not encode proteins (‘noncoding RNAs’) but which, nevertheless, exert powerful effects on gene expression at both transcriptional and posttranscriptional levels. Our late colleague Biao Ding, who died unexpectedly on June 25, 2015, proposed a Focus Issue on the roles in plant-microbe interactions of noncoding RNAs, whether of plant or microbial origin and including small interfering (si)RNAs, microRNAs, phased siRNAs, and long noncoding RNAs, as well as viroids and satellite RNAs. The Editorial Board of MPMI has decided to dedicate this Focus Issue to the memory of Professor Biao Ding, a valued and deeply missed colleague and friend.

scholarly journals Transvection and pairing of a Drosophila Hox long noncoding RNA in the regulation of Sex combs reduced

2016 ◽  
Author(s):  
Tom Pettini ◽  
Matthew Ronshaugen
Keyword(s):  
Gene Expression ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Early Embryo ◽  
Long Noncoding Rnas ◽  
Regulatory Sequences ◽  
Sex Combs Reduced ◽  
Hox Gene ◽  
Sex Combs

ABSTRACTLong noncoding RNAs have emerged as abundant and important regulators of gene expression in diverse animals. In D. melanogaster several lncRNAs involved in regulating Hox gene expression in the Bithorax Complex have been reported. However, no functional Hox long noncoding RNAs have been described in the Antennapedia Complex. Here we have characterized a long noncoding RNA lincX from the Antennapedia Complex, that is transcribed from previously identified cis-regulatory sequences of the Hox gene Sex combs reduced (Scr). We use both the GAL4-UAS system and mutants to ectopically overexpress the lincX RNA from exogenous and endogenous loci respectively, in order to dissect the potential regulatory functions of lincX RNA versus lincX transcription. Our findings suggest that transcription through the lincX locus, but not the lincX RNA itself, may facilitate initiation of Scr in cis in the early embryo. Transvection phenomena, where regulatory sequences on one chromosome can affect expression on the homolog, have previously been reported in genetic studies of Scr. By analysing lincX and Scr nascent transcriptional sites in embryos heterozygous for a gain of function mutation, we directly visualize this transvection, and observe that the ectopic lincX transcriptional state appears to be relayed in trans to the homologous wild-type chromosome. This trans-activation of lincX correlates with both ectopic activation of Scr in cis, and increased chromosomal proximity. Our results are consistent with a model whereby early long noncoding RNA transcription through cis-regulatory sequences can be communicated between chromosomes, and facilitates long-range initiation of Hox gene expression in cis.

scholarly journals The Challenges and Opportunities in the Clinical Application of Noncoding RNAs: The Road Map for miRNAs and piRNAs in Cancer Diagnostics and Prognostics

2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Preethi Krishnan ◽  
Sambasivarao Damaraju
Keyword(s):  
Gene Expression ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Cancer Diagnostics ◽  
Master Regulators ◽  
The Road ◽  
Small Noncoding Rnas ◽  
Road Map ◽  
Challenges And Opportunities ◽  
Compare And Contrast

Discoveries on nonprotein-coding RNAs have induced a paradigm shift in our overall understanding of gene expression and regulation. We now understand that coding and noncoding RNA machinery work in concert to maintain overall homeostasis. Based on their length, noncoding RNAs are broadly classified into two groups—long (>200 nt) and small noncoding RNAs (<200 nt). These RNAs perform diverse functions—gene regulation, splicing, translation, and posttranscriptional modifications. MicroRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs) are two classes of small noncoding RNAs that are now classified as master regulators of gene expression. They have also demonstrated clinical significance as potential biomarkers and therapeutic targets for several diseases, including cancer. Despite these similarities, both these RNAs are generated through contrasting mechanisms, and one of the aims of this review is to cover the distance travelled since their discovery and compare and contrast the various facets of these RNAs. Although these RNAs show tremendous promise as biomarkers, translating the findings from bench to bedside is often met with roadblocks. The second aim of this review therefore is to highlight some of the challenges that hinder application of miRNA and piRNA as in guiding treatment decisions.

scholarly journals PVT1: A Rising Star among Oncogenic Long Noncoding RNAs

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Teresa Colombo ◽  
Lorenzo Farina ◽  
Giuseppe Macino ◽  
Paola Paci
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Functional Characterization ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Competing Endogenous Rna ◽  
Protein Coding ◽  
Myc Oncogene ◽  
Non Coding Rnas

It is becoming increasingly clear that short and long noncoding RNAs critically participate in the regulation of cell growth, differentiation, and (mis)function. However, while the functional characterization of short non-coding RNAs has been reaching maturity, there is still a paucity of well characterized long noncoding RNAs, even though large studies in recent years are rapidly increasing the number of annotated ones. The long noncoding RNA PVT1 is encoded by a gene that has been long known since it resides in the well-known cancer risk region 8q24. However, a couple of accidental concurrent conditions have slowed down the study of this gene, that is, a preconception on the primacy of the protein-coding over noncoding RNAs and the prevalent interest in its neighbor MYC oncogene. Recent studies have brought PVT1 under the spotlight suggesting interesting models of functioning, such as competing endogenous RNA activity and regulation of protein stability of important oncogenes, primarily of the MYC oncogene. Despite some advancements in modelling the PVT1 role in cancer, there are many questions that remain unanswered concerning the precise molecular mechanisms underlying its functioning.

scholarly journals Emerging evidence on noncoding-RNA regulatory machinery in intervertebral disc degeneration: a narrative review

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Hao-Yu Guo ◽  
Ming-Ke Guo ◽  
Zhong-Yuan Wan ◽  
Fang Song ◽  
Hai-Qiang Wang
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Noncoding Rna ◽  
Regulatory Networks ◽  
Intervertebral Disc Degeneration ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Circular Rnas ◽  
Form Complex ◽  
Underlying Mechanisms

AbstractIntervertebral disc degeneration (IDD) is the most common cause of low-back pain. Accumulating evidence indicates that the expression profiling of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long noncoding RNAs (lncRNAs), are different between intervertebral disc tissues obtained from healthy individuals and patients with IDD. However, the roles of ncRNAs in IDD are still unclear until now. In this review, we summarize the studies concerning ncRNA interactions and regulatory functions in IDD. Apoptosis, aberrant proliferation, extracellular matrix degradation, and inflammatory abnormality are tetrad fundamental pathologic phenotypes in IDD. We demonstrated that ncRNAs are playing vital roles in apoptosis, proliferation, ECM degeneration, and inflammation process of IDD. The ncRNAs participate in underlying mechanisms of IDD in different ways. MiRNAs downregulate target genes’ expression by directly binding to the 3′-untranslated region of mRNAs. CircRNAs and lncRNAs act as sponges or competing endogenous RNAs by competitively binding to miRNAs and regulating the expression of mRNAs. The lncRNAs, circRNAs, miRNAs, and mRNAs widely crosstalk and form complex regulatory networks in the degenerative processes. The current review presents novel insights into the pathogenesis of IDD and potentially sheds light on the therapeutics in the future.

scholarly journals Long Noncoding RNAs-Related Diseases, Cancers, and Drugs

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jen-Yang Tang ◽  
Jin-Ching Lee ◽  
Yung-Ting Chang ◽  
Ming-Feng Hou ◽  
Hurng-Wern Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Natural Products ◽  
Long Noncoding Rna ◽  
Regulatory Network ◽  
Noncoding Rna ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Related Gene ◽  
Gene Expressions ◽  
Clinical Drugs

Long noncoding RNA (lncRNA) function is described in terms of related gene expressions, diseases, and cancers as well as their polymorphisms. Potential modulators of lncRNA function, including clinical drugs, natural products, and derivatives, are discussed, and bioinformatic resources are summarized. The improving knowledge of the lncRNA regulatory network has implications not only in gene expression, diseases, and cancers, but also in the development of lncRNA-based pharmacology.

scholarly journals miR in melanoma development: miRNAs and acquired hallmarks of cancer in melanoma

2013 ◽  
Vol 45 (22) ◽  
pp. 1049-1059 ◽  
Author(s):  
Paige E. Bennett ◽  
Lynne Bemis ◽  
David A. Norris ◽  
Yiqun G. Shellman
Keyword(s):  
Gene Expression ◽  
Systematic Review ◽  
Therapeutic Potential ◽  
Noncoding Rnas ◽  
Review Of The Literature ◽  
Cancer Model ◽  
Hallmarks Of Cancer ◽  
Regulate Gene Expression ◽  
Small Noncoding Rnas ◽  
Regulate Gene

Melanoma is a very aggressive skin cancer with increasing incidence worldwide. MicroRNAs are small, noncoding RNAs that regulate gene expression of targeted gene(s). The hallmark of cancer model outlined by Hanahan and Weinberg offers a meaningful framework to consider the roles of microRNAs in melanoma development and progression. In this systematic review of the literature, we associate what is known about deregulation of microRNAs and their targeted genes in melanoma development with the hallmarks and characteristics of cancer. The diagnostic and therapeutic potential of microRNAs for future melanoma management will also be discussed.

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