scholarly journals Role of Non-coding RNA in Acetaminophen-induced Liver Injury

2021 ◽  
Author(s):  
Vivek Chowdhary ◽  
Pipasha Biswas ◽  
Kalpana Ghoshal
Keyword(s):  
Liver Injury ◽  
Liver Toxicity ◽  
Circular Rnas ◽  
Regulation Of Expression ◽  
Stem Loop ◽  
Stem Loop Structure ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Regulatory Rnas

Genomic and transcriptomic analyses have well established that the major fraction of the mammalian genome is transcribed into different classes of RNAs ranging in size from a few nucleotides to hundreds of thousands of nucleotides, which do not encode any protein. Some of these non-coding RNAs (ncRNAs) are directly or indirectly linked to the regulation of expression or functions of ~25,000 proteins coded by <2% of the human genome. Among these regulatory RNAs, microRNAs are small (21-25 nucleotide) RNAs that are processed from precursor RNAs that have stem-loop structure, whereas non-coding RNAs >200 nucleotides are termed lncRNAs (long ncRNAs). Circular RNAs (circRNAs) are newly identified lncRNA members that are generated by back-splicing of primary transcripts. The functions of ncRNAs in modulating liver toxicity of xenobiotics are emerging only recently. Acetaminophen (N-acetyl-para-aminophenol, paracetamol or APAP) is a safe analgesic and antipyretic drug at the therapeutic dose. However, it can cause severe liver toxicity that may lead to liver failure if overdosed or combined with alcohol, herbs, or other xenobiotics. This review discusses the role of ncRNAs in acetaminophen metabolism, toxicity, and liver regeneration after APAP - induced liver injury (AILI).

scholarly journals Circular RNA-Centered Regulatory Networks in the Physiopathology of Cardiovascular Diseases

2020 ◽  
Vol 21 (2) ◽  
pp. 456 ◽  
Author(s):  
André F. Gabriel ◽  
Marina C. Costa ◽  
Francisco J. Enguita
Keyword(s):  
Cardiovascular Diseases ◽  
Cell Biology ◽  
Regulatory Networks ◽  
Current Knowledge ◽  
Circular Rna ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Regulatory Rnas ◽  
Eukaryotic Genomes

Non-coding regulatory RNAs are generated as a core output of the eukaryotic genomes, being essential players in cell biology. At the organism level, they are key functional actors in those tissues and organs with limited proliferation capabilities such as the heart. The role of regulatory networks mediated by non-coding RNAs in the pathophysiology of cardiovascular conditions is starting to be unveiled. However, a deeper knowledge of the functional interactions among the diverse non-coding RNA families and their phenotypic consequences is required. This review presents the current knowledge about the functional crosstalk between circRNAs and other biomolecules in the framework of the cardiovascular diseases.

scholarly journals Exosomal microRNAs and other non-coding RNAs as colorectal cancer biomarkers: a review

Mutagenesis ◽  
2019 ◽  
Vol 35 (3) ◽  
pp. 243-260 ◽  
Author(s):  
Antonio Francavilla ◽  
Szimonetta Turoczi ◽  
Sonia Tarallo ◽  
Pavel Vodicka ◽  
Barbara Pardini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Expression Profiles ◽  
Predictive Markers ◽  
Circular Rnas ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Prognostic And Predictive Markers

Abstract The circulating human transcriptome, which includes both coding and non-coding RNA (ncRNA) molecules, represents a rich source of potential biomarkers for colorectal cancer (CRC) that has only recently been explored. In particular, the release of RNA-containing extracellular vesicles (EVs), in a multitude of different in vitro cell systems and in a variety of body fluids, has attracted wide interest. The role of RNA species in EVs is still not fully understood, but their capacity to act as a form of distant communication between cells and their higher abundance in association with cancer demonstrated their relevance. In this review, we report the evidence from both in vitro and human studies on microRNAs (miRNAs) and other ncRNA profiles analysed in EVs in relation to CRC as diagnostic, prognostic and predictive markers. The studies so far highlighted that, in exosomes, the most studied category of EVs, several miRNAs are able to accurately discriminate CRC cases from controls as well as to describe the progression of the disease and its prognosis. Most of the time, the in vitro findings support the miRNA profiles detected in human exosomes. The expression profiles measured in exosomes and other EVs differ and, interestingly, there is a variability of expression also among different subsets of exosomes according to their proteic profile. On the other hand, evidence is still limited for what concerns exosome miRNAs as early diagnostic and predictive markers of treatment. Several other ncRNAs that are carried by exosomes, mostly long ncRNAs and circular RNAs, seem also to be dysregulated in CRC. Besides various technical challenges, such as the standardisation of EVs isolation methods and the optimisation of methodologies to characterise the whole spectrum of RNA molecules in exosomes, further studies are needed in order to elucidate their relevance as CRC markers.

scholarly journals Terminal uridyltransferase 7 regulates TLR4-triggered inflammation by controlling Regnase-1 mRNA uridylation and degradation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chia-Ching Lin ◽  
Yi-Ru Shen ◽  
Chi-Chih Chang ◽  
Xiang-Yi Guo ◽  
Yun-Yun Young ◽  
...  
Keyword(s):  
Posttranscriptional Regulation ◽  
Inflammatory Responses ◽  
Rna Stability ◽  
Innate Immune ◽  
Stem Loop ◽  
Stem Loop Structure ◽  
Tlr4 Activation ◽  
Harmful Effects ◽  
Different Levels

AbstractDifferent levels of regulatory mechanisms, including posttranscriptional regulation, are needed to elaborately regulate inflammatory responses to prevent harmful effects. Terminal uridyltransferase 7 (TUT7) controls RNA stability by adding uridines to its 3′ ends, but its function in innate immune response remains obscure. Here we reveal that TLR4 activation induces TUT7, which in turn selectively regulates the production of a subset of cytokines, including Interleukin 6 (IL-6). TUT7 regulates IL-6 expression by controlling ribonuclease Regnase-1 mRNA (encoded by Zc3h12a gene) stability. Mechanistically, TLR4 activation causes TUT7 to bind directly to the stem-loop structure on Zc3h12a 3′-UTR, thereby promotes Zc3h12a uridylation and degradation. Zc3h12a from LPS-treated TUT7-sufficient macrophages possesses increased oligo-uridylated ends with shorter poly(A) tails, whereas oligo-uridylated Zc3h12a is significantly reduced in Tut7-/- cells after TLR4 activation. Together, our findings reveal the functional role of TUT7 in sculpting TLR4-driven responses by modulating mRNA stability of a selected set of inflammatory mediators.

scholarly journals Identification and characterization of a sequence motif involved in nonsense-mediated mRNA decay.

1995 ◽  
Vol 15 (4) ◽  
pp. 2231-2244 ◽  
Author(s):  
S Zhang ◽  
M J Ruiz-Echevarria ◽  
Y Quan ◽  
S W Peltz
Keyword(s):  
Mrna Decay ◽  
Sequence Motif ◽  
Nonsense Mutations ◽  
Stem Loop ◽  
Cis Acting ◽  
Stem Loop Structure ◽  
Nonsense Codon ◽  
Nonsense Mediated Mrna Decay

In both prokaryotes and eukaryotes, nonsense mutations in a gene can enhance the decay rate or reduce the abundance of the mRNA transcribed from that gene, and we call this process nonsense-mediated mRNA decay. We have been investigating the cis-acting sequences involved in this decay pathway. Previous experiments have demonstrated that, in addition to a nonsense codon, specific sequences 3' of a nonsense mutation, which have been defined as downstream elements, are required for mRNA destabilization. The results presented here identify a sequence motif (TGYYGATGYYYYY, where Y stands for either T or C) that can predict regions in genes that, when positioned 3' of a nonsense codon, promote rapid decay of its mRNA. Sequences harboring two copies of the motif from five regions in the PGK1, ADE3, and HIS4 genes were able to function as downstream elements. In addition, four copies of this motif can function as an independent downstream element. The sequences flanking the motif played a more significant role in modulating its activity when fewer copies of the sequence motif were present. Our results indicate the sequences 5' of the motif can modulate its activity by maintaining a certain distance between the sequence motif and the termination codon. We also suggest that the sequences 3' of the motif modulate the activity of the downstream element by forming RNA secondary structures. Consistent with this view, a stem-loop structure positioned 3' of the sequence motif can enhance the activity of the downstream element. This sequence motif is one of the few elements that have been identified that can predict regions in genes that can be involved in mRNA turnover. The role of these sequences in mRNA decay is discussed.

scholarly journals Essential Role of Non-Coding RNAs in Enterovirus Infection: From Basic Mechanisms to Clinical Prospects

2021 ◽  
Vol 22 (6) ◽  
pp. 2904
Author(s):  
Peiyu Zhu ◽  
Shuaiyin Chen ◽  
Weiguo Zhang ◽  
Guangcai Duan ◽  
Yuefei Jin
Keyword(s):  
Acute Flaccid Paralysis ◽  
Foot And Mouth Disease ◽  
Human Diseases ◽  
Circular Rnas ◽  
Enterovirus Infection ◽  
Research Directions ◽  
Cardiorespiratory Failure ◽  
New Ideas ◽  
Non Coding Rnas

Enteroviruses (EVs) are common RNA viruses that can cause various types of human diseases and conditions such as hand, foot, and mouth disease (HFMD), myocarditis, meningitis, sepsis, and respiratory disorders. Although EV infections in most patients are generally mild and self-limiting, a small number of young children can develop serious complications such as encephalitis, acute flaccid paralysis, myocarditis, and cardiorespiratory failure, resulting in fatalities. Established evidence has suggested that certain non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) are involved in the occurrence and progression of many human diseases. Recently, the involvement of ncRNAs in the course of EV infection has been reported. Herein, the authors focus on recent advances in the understanding of ncRNAs in EV infection from basic viral pathogenesis to clinical prospects, providing a reference basis and new ideas for disease prevention and research directions.

sRNA STnc150 is involved in virulence regulation of Salmonella Typhimurium by targeting fimA mRNA

2021 ◽  
Vol 368 (18) ◽  
Author(s):  
Jing Li ◽  
Na Li ◽  
Chengcheng Ning ◽  
Yun Guo ◽  
Chunhui Ji ◽  
...  
Keyword(s):  
Salmonella Typhimurium ◽  
Target Genes ◽  
Reporter System ◽  
Stem Loop ◽  
Viral Loads ◽  
Virulence Regulation ◽  
Stem Loop Structure ◽  
Complementary Strain

ABSTRACT Small RNAs (sRNAs) are essential virulent regulators in Salmonella typhimurium (STM). To explore the role of sRNA STnc150 in regulating STM virulence, we constructed a STnc150 deletion strain (ΔSTnc150) and its complementary strain (ΔSTnc150/C). Then, we compared their characteristics to their original parent strain experimentally, identified the target genes of STnc150 and determined the expression levels of target genes. The results showed that the ΔSTnc150 strain exhibited delayed biofilm formation, enhanced adhesion to macrophages, significantly reduced LD50, increased liver and spleen viral loads and more vital pathological damaging ability than its parent and complementary strains. Further, bioinformatics combined with the bacterial dual plasmid reporter system confirmed that the bases 72–88 of STnc150 locating at the secondary stem-loop structure of the STnc150 are complementary with the bases 1–19 in the 5′-terminal of fimA mRNA of the type 1 fimbriae subunit. Western blot analysis showed that fimA protein level was increased in STnc150 strain compared with its parent and complementary strains. Together, this study suggested that STnc150 can down-regulate STM fimA expression at the translation level, which provided insights into the regulatory mechanisms of sRNAs in virulence of STM.

scholarly journals Non-Coding RNA in Acute Ischemic Stroke: Mechanisms, Biomarkers and Therapeutic Targets

2018 ◽  
Vol 27 (12) ◽  
pp. 1763-1777 ◽  
Author(s):  
Sheng-Wen Wang ◽  
Zhong Liu ◽  
Zhong-Song Shi
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Neural Development ◽  
Therapeutic Targets ◽  
Circular Rnas ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Cerebral Ischemic ◽  
Functional Rnas ◽  
The Brain

Non-coding RNAs (ncRNAs) are a class of functional RNAs that regulate gene expression in a post-transcriptional manner. NcRNAs include microRNAs, long non-coding RNAs and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes, including cerebral ischemic injury, neurodegeneration, neural development, and plasticity. Stroke is one of the leading causes of death and physical disability worldwide. Acute ischemic stroke (AIS) occurs when brain blood flow stops, and that stoppage results in reduced oxygen and glucose supply to cells in the brain. In this article, we review the latest progress on ncRNAs in relation to their implications in AIS, as well as their potential as diagnostic and prognostic biomarkers. We also review ncRNAs acting as possible therapeutic targets in future precision medicine. Finally, we conclude with a brief discussion of current challenges and future directions for ncRNAs studies in AIS, which may facilitate the translation of ncRNAs research into clinical practice to improve clinical outcome of AIS.

scholarly journals Emerging role of a novel small non-coding regulatory RNA: tRNA-derived small RNA

ExRNA ◽  
2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Fangfang Jin ◽  
Zhigang Guo
Keyword(s):  
Small Rna ◽  
Current Knowledge ◽  
Future Research ◽  
Regulatory Rna ◽  
Biological Functions ◽  
Research Directions ◽  
Non Coding Rna ◽  
Future Research Directions ◽  
Non Coding Rnas

Abstract The discovery of small non-coding RNAs, such as miRNA and piRNA, has dramatically changed our understanding of the role RNA plays in organisms. Recent studies show that a novel small non-coding RNA generated from cleavage of tRNA or pre-tRNA, called tRNA-derived small RNA (tsRNA), serves as a new regulator of gene expression. tsRNA has been determined participate in regulating some specific physiological and pathological processes. Although knowledge regarding the biological roles of miRNA and piRNA is expanding, whether tsRNAs play similar roles remains poorly understood. Here, we review the current knowledge regarding the mechanisms of action and biological functions of tsRNAs in intracellular, extracellular and intergenerational inheritance, and highlight the potential application of tsRNAs in human diseases, and present the current problems and future research directions.

scholarly journals Long Non-coding RNA XIST Attenuates Diabetic Peripheral Neuropathy by Inducing Autophagy Through MicroRNA-30d-5p/sirtuin1 Axis

2021 ◽  
Vol 8 ◽  
Author(s):  
Bei-Yan Liu ◽  
Lin Li ◽  
Li-Wei Bai ◽  
Chang-Shui Xu
Keyword(s):  
Oxidative Stress ◽  
Peripheral Neuropathy ◽  
Schwann Cells ◽  
Diabetic Peripheral Neuropathy ◽  
Beclin 1 ◽  
Diabetic Mice ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Diabetic peripheral neuropathy (DPN) is a prevalent diabetes mellitus (Feldman et al., 2017) complication and the primary reason for amputation. Meanwhile, long non-coding RNAs (lncRNAs) are a type of regulatory non-coding RNAs (ncRNAs) that broadly participate in DPN development. However, the correlation of lncRNA X-inactive specific transcript (XIST) with DPN remains unclear. In this study, we were interested in the role of XIST in the modulation of DPN progression. Significantly, our data showed that the expression of XIST and sirtuin1 (SIRT1) was inhibited, and the expression of microRNA-30d-5p (miR-30d-5p) was enhanced in the trigeminal sensory neurons of the diabetic mice compared with the normal mice. The levels of LC3II and Beclin-1 were inhibited in the diabetic mice. The treatment of high glucose (HG) reduced the XIST expression in Schwann cells. The apoptosis of Schwann cells was enhanced in the HG-treated cells, but the overexpression of XIST could block the effect in the cells. Moreover, the levels of LC3II and Beclin-1 were reduced in the HG-treated Schwann cells, while the overexpression of XIST was able to reverse this effect. The HG treatment promoted the production of oxidative stress, while the XIST overexpression could attenuate this result in the Schwann cells. Mechanically, XIST was able to sponge miR-30d-5p and miR-30d-5p-targeted SIRT1 in the Schwann cells. MiR-30d-5p inhibited autophagy and promoted oxidative stress in the HG-treated Schwann cells, and SIRT1 presented a reversed effect. MiR-30d-5p mimic or SIRT1 depletion could reverse XIST overexpression-mediated apoptosis and autophagy of the Schwann cells. Thus, we concluded that XIST attenuated DPN by inducing autophagy through miR-30d-5p/SIRT1 axis. XIST and miR-30d-5p may be applied as the potential targets for DPN therapy.

scholarly journals CircRNAs and their regulatory roles in cancers

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Mei Tao ◽  
Ming Zheng ◽  
Yanhua Xu ◽  
Shuo Ma ◽  
Weiwei Zhang ◽  
...  
Keyword(s):  
Nuclear Export ◽  
Mrna Translation ◽  
High Sensitivity ◽  
Detection Methods ◽  
Circular Rnas ◽  
Rnase L ◽  
Circular Structure ◽  
Dynamic Modification ◽  
Non Coding Rnas

AbstractCircular RNAs (circRNAs), a novel type of non-coding RNAs (ncRNAs), have a covalently closed circular structure resulting from pre-mRNA back splicing via spliceosome and ribozymes. They can be classified differently in accordance with different criteria. As circRNAs are abundant, conserved, and stable, they can be used as diagnostic markers in various diseases and targets to develop new therapies. There are various functions of circRNAs, including sponge for miR/proteins, role of scaffolds, templates for translation, and regulators of mRNA translation and stability. Without m7G cap and poly-A tail, circRNAs can still be degraded in several ways, including RNase L, Ago-dependent, and Ago-independent degradation. Increasing evidence indicates that circRNAs can be modified by N-6 methylation (m6A) in many aspects such as biogenesis, nuclear export, translation, and degradation. In addition, they have been proved to play a regulatory role in the progression of various cancers. Recently, methods of detecting circRNAs with high sensitivity and specificity have also been reported. This review presents a detailed overview of circRNAs regarding biogenesis, biomarker, functions, degradation, and dynamic modification as well as their regulatory roles in various cancers. It’s particularly summarized in detail in the biogenesis of circRNAs, regulation of circRNAs by m6A modification and mechanisms by which circRNAs affect tumor progression respectively. Moreover, existing circRNA detection methods and their characteristics are also mentioned.

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