scholarly journals Functional Interplay between RNA Viruses and Non-Coding RNA in Mammals

2019 ◽  
Vol 5 (1) ◽  
pp. 7 ◽  
Author(s):  
Nkerorema Djodji Damas ◽  
Nicolas Fossat ◽  
Troels K. H. Scheel
Keyword(s):  
Metabolic Pathways ◽  
Mammalian Cells ◽  
Rna Viruses ◽  
Rna Virus ◽  
Messenger Rnas ◽  
Host Interactions ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Antiviral Targets ◽  
Replicative Cycle

Exploring virus–host interactions is key to understand mechanisms regulating the viral replicative cycle and any pathological outcomes associated with infection. Whereas interactions at the protein level are well explored, RNA interactions are less so. Novel sequencing methodologies have helped uncover the importance of RNA–protein and RNA–RNA interactions during infection. In addition to messenger RNAs (mRNAs), mammalian cells express a great number of regulatory non-coding RNAs, some of which are crucial for regulation of the immune system whereas others are utilized by viruses. It is thus becoming increasingly clear that RNA interactions play important roles for both sides in the arms race between virus and host. With the emerging field of RNA therapeutics, such interactions are promising antiviral targets. In this review, we discuss direct and indirect RNA interactions occurring between RNA viruses or retroviruses and host non-coding transcripts upon infection. In addition, we review RNA virus derived non-coding RNAs affecting immunological and metabolic pathways of the host cell typically to provide an advantage to the virus. The relatively few known examples of virus–host RNA interactions suggest that many more await discovery.

scholarly journals BPIFB3 interacts with ARFGAP1 and TMED9 to regulate non-canonical autophagy and RNA virus infection

2020 ◽  
pp. jcs.251835
Author(s):  
Azia S. Evans ◽  
Nicholas J. Lennemann ◽  
Carolyn B. Coyne
Keyword(s):  
Mass Spectrometry ◽  
Mammalian Cells ◽  
Viral Infections ◽  
Rna Viruses ◽  
Rna Virus ◽  
Negative Regulator ◽  
Host Factors ◽  
Important Negative Regulator ◽  
Cellular Components

Autophagy is a degradative cellular pathway that targets cytoplasmic contents and organelles for turnover by the lysosome. Various autophagy pathways play key roles in the clearance of viral infections, and many families of viruses have developed unique methods for avoiding degradation. Some positive stranded RNA viruses, such as enteroviruses and flaviviruses, usurp the autophagic pathway to promote their own replication. We previously identified the endoplasmic reticulum-localized protein BPIFB3 as an important negative regulator of non-canonical autophagy that uniquely impacts the replication of enteroviruses and flaviviruses. Here, we find that many components of the canonical autophagy machinery are not required for BPIFB3 depletion induced autophagy and identify the host factors that facilitate its role in the replication of enteroviruses and flaviviruses. Using proximity-dependent biotinylation (BioID) followed by mass spectrometry, we identify ARFGAP1 and TMED9 as two cellular components that interact with BPIFB3 to regulate autophagy and viral replication. Importantly, our data demonstrate that non-canonical autophagy in mammalian cells can be controlled outside of the traditional pathway regulators and define the role of two proteins in BPIFB3 depletion mediated non-canonical autophagy.

scholarly journals An overview of RNA virus-encoded microRNAs

ExRNA ◽  
2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Xihan Li ◽  
Xiaoping Zou
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Viral Replication ◽  
Potential Role ◽  
Rna Viruses ◽  
Rna Virus ◽  
Host Cells ◽  
Basic Pattern ◽  
Double Stranded Dna ◽  
Non Coding Rnas

Abstract MicroRNAs (miRNAs) are a number of small non-coding RNAs playing a regulatory part in gene expression. Many virus-encoded miRNAs have been found, which manifests that viruses as well apply the basic pattern of gene regulation, however, mostly in viruses transcribed from double-stranded DNA genomes. It is still in dispute if RNA viruses could encode miRNAs because the excision of miRNA might result in the cleavage of viral RNA genome. We will focus on the miRNAs encoded by RNA virus and discuss their potential role in viral replication cycle and host cells.

scholarly journals Identification of Non-coding RNA Biomarkers in Stress-induced Depression via Comprehensive Analysis of Competing Endogenous RNA Network

2020 ◽  
Author(s):  
xuanjun liu ◽  
Lan Yan ◽  
Chun Lin ◽  
Yiliang Zhang ◽  
Haofei Miao ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Comprehensive Analysis ◽  
Differentially Expressed ◽  
Psychiatric Disease ◽  
Circular Rnas ◽  
Messenger Rnas ◽  
Competing Endogenous Rna ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Promising Perspective

Abstract BackgroundDepression is one of the most common psychiatric disease worldwide. Although the research about the pathogenesis of depression have achieved progress, the detailed effect of non-coding RNAs (ncRNAs) in depression are still not clearly elucidated. This study was aimed to identify non-coding RNA biomarkers in stress-induced depression via comprehensive analysis of competing endogenous RNA networkMethodsIn this present study, we acquired RNA expression from RNA seq expression profile in three mice with depressive-like behaviors using chronic restraint stress paradigm and three C57BL/6J wild-type mice as control mice. ResultsA total of 41 differentially expressed circular RNAs (circRNAs) and 181 differentially expressed messenger RNAs (mRNAs) were up-regulated, and 65 differentially expressed circRNAs and 289 differentially expressed mRNAs were down-regulated, which were selected by a threshold of fold change ≥2 and a p-value < 0.05. Gene Ontology was performed to analyze the biological functions, and we predicted potential signaling pathways based on Kyoto Encyclopedia of Genes and Genomes pathway database. In addition, we constructed a circRNA-microRNA (miRNA)-mRNA regulatory network to further identify non-coding RNAs biomarkers. ConclusionsOur findings provide a promising perspective for further research into molecular mechanisms of depression, and targeting circRNA -mediated competing endogenous RNA (ceRNA) network is a useful strategy to early recognize the depression.

scholarly journals The Multifunctional Long-Distance Movement Protein of Pea Enation Mosaic Virus 2 Protects Viral and Host Transcripts from Nonsense-Mediated Decay

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Jared P. May ◽  
Philip Z. Johnson ◽  
Muhammad Ilyas ◽  
Feng Gao ◽  
Anne E. Simon
Keyword(s):  
Mosaic Virus ◽  
Rna Viruses ◽  
Rna Virus ◽  
Messenger Rnas ◽  
Rna Seq ◽  
Long Distance ◽  
Content Type ◽  
Nonsense Mediated Decay ◽  
Long Distance Movement ◽  
Pea Enation Mosaic Virus

ABSTRACT The nonsense-mediated decay (NMD) pathway presents a challenge for RNA viruses with termination codons that precede extended 3′ untranslated regions (UTRs). The umbravirus Pea enation mosaic virus 2 (PEMV2) is a nonsegmented, positive-sense RNA virus with an unusually long 3′ UTR that is susceptible to NMD. To establish a systemic infection, the PEMV2 long-distance movement protein p26 was previously shown to both stabilize viral RNAs and bind them for transport through the plant’s vascular system. The current study demonstrated that p26 protects both viral and nonviral messenger RNAs from NMD. Although p26 localizes to both the cytoplasm and nucleolus, p26 exerts its anti-NMD effects exclusively in the cytoplasm independently of long-distance movement. Using a transcriptome-wide approach in the model plant Nicotiana benthamiana, p26 protected a subset of cellular NMD target transcripts, particularly those containing long, structured, GC-rich 3′ UTRs. Furthermore, transcriptome sequencing (RNA-seq) revealed that the NMD pathway is highly dysfunctional during PEMV2 infection, with 1,820 (48%) of NMD targets increasing in abundance. Widespread changes in the host transcriptome are common during plant RNA virus infections, and these results suggest that, in at least some instances, virus-mediated NMD inhibition may be a major contributing factor. IMPORTANCE Nonsense-mediated decay (NMD) represents an RNA regulatory pathway that degrades both natural and faulty messenger RNAs with long 3′ untranslated regions. NMD targets diverse families of RNA viruses, requiring that viruses counteract the NMD pathway for successful amplification in host cells. A protein required for long-distance movement of Pea enation mosaic virus 2 (PEMV2) is shown to also protect both viral and host mRNAs from NMD. RNA-seq analyses of the Nicotiana benthamiana transcriptome revealed that PEMV2 infection significantly impairs the host NMD pathway. RNA viruses routinely induce large-scale changes in host gene expression, and, like PEMV2, may use NMD inhibition to alter the host transcriptome in an effort to increase virus amplification.

scholarly journals Comprehensive Analysis of lncRNA–miRNA– mRNA Network Ascertains Prognostic Factors in Patients with Colon Cancer

2019 ◽  
Vol 18 ◽  
pp. 153303381985323 ◽  
Author(s):  
Zhenzhen Gao ◽  
Peng Fu ◽  
Zhengyi Yu ◽  
Fuxi Zhen ◽  
Yanhong Gu
Keyword(s):  
Colon Cancer ◽  
Gene Ontology ◽  
Differentially Expressed ◽  
Messenger Rnas ◽  
Competing Endogenous Rna ◽  
Normal Colon ◽  
Kaplan Meier ◽  
Non Coding Rna ◽  
Competing Endogenous Rnas ◽  
Non Coding Rnas

Background: Non-coding RNAs are competing endogenous RNAs in the occurrence and development of tumorigenesis; numerous microRNAs are aberrantly expressed in colon cancer tissues and play significant roles in oncogenesis development and metastasis. However, large clinical and RNA data are lacking to further confirm the exact role of these RNAs in tumors. This study aimed to ascertain differential RNA expression between colon cancer and normal colon tissues. Materials and Methods: RNA sequencing and clinical data of patients with colon cancer were procured from The Cancer Genome Atlas database; differentially expressed long non-coding RNA, differentially expressed messenger RNAs, and differentially expressed microRNAs were achieved using the limma package in edgeR to generate competing endogenous RNAs networks. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted with ggplot2 package, the Kaplan-Meier survival method was used to predict survival in patients with colon cancer. Results: In total, 1174 differentially expressed long non-coding RNAs, 2068 differentially expressed messenger RNAs, and 239 differentially expressed microRNAs were generated between 480 colon cancer and 41 normal colon tissue samples. Three competing endogenous RNA networks were established. Gene Ontology analysis indicated that the genes of the up-regulated microRNA network were involved in negative regulation of transcription, DNA-template, and those of down-regulated microRNA network were involved in transforming growth factor β receptor signaling pathways, response to hypoxia, cell migration, while Kyoto Encyclopedia of Genes and Genomes analyses of these networks turned out to be negative. Three long non-coding RNAs (AP004609.1, ARHGEF26-AS1, and LINC00491), 3 microRNAs (miRNA-141, miRNA-216a, and miRNA-193b) and 3 RNAs (ULBP2, PHLPP2, and TPM2) were detected to be associated with prognosis by the Kaplan-Meier survival analysis. Additionally, univariate and multivariate Cox regression analyses showed that the microRNA-216a of the competing endogenous RNA might be an independent prognostic factor in colon cancer. Conclusions: This study constructed the non-coding RNA-related competing endogenous RNA networks in colon cancer and sheds lights on underlying biomarkers for colon cancer cohorts.

scholarly journals Main N6-Methyladenosine Readers: YTH Family Proteins in Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin-Yuan Dai ◽  
Liang Shi ◽  
Zhi Li ◽  
Hai-Yan Yang ◽  
Ji-Fu Wei ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Rna Splicing ◽  
Mammalian Cells ◽  
Biological Function ◽  
Human Cancer ◽  
Messenger Rnas ◽  
Rna Modifications ◽  
Reversible Process ◽  
Rna Export ◽  
Non Coding Rnas

Among the over 150 RNA modifications, N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic RNAs, not only in messenger RNAs, but also in microRNAs and long non-coding RNAs. It is a dynamic and reversible process in mammalian cells, which is installed by “writers,” consisting of METTL3, METTL14, WTAP, RBM15/15B, and KIAA1429 and removed by “erasers,” including FTO and ALKBH5. Moreover, m6A modification is recognized by “readers,” which play the key role in executing m6A functions. IYT521-B homology (YTH) family proteins are the first identified m6A reader proteins. They were reported to participate in cancer tumorigenesis and development through regulating the metabolism of targeted RNAs, including RNA splicing, RNA export, translation, and degradation. There are many reviews about function of m6A and its role in various diseases. However, reviews only focusing on m6A readers, especially YTH family proteins are few. In this review, we systematically summarize the recent advances in structure and biological function of YTH family proteins, and their roles in human cancer and potential application in cancer therapy.

scholarly journals Identification and targeting of G-quadruplex structures in MALAT1 long non-coding RNA

2021 ◽  
Author(s):  
Xi Mou ◽  
Shiau Wei Liew ◽  
Chun Kit Kwok
Keyword(s):  
High Specificity ◽  
Messenger Rnas ◽  
Functional Roles ◽  
Cellular Processes ◽  
Multiple Strategies ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Nuclear Cell

RNA G-quadruplexes (rG4s) have functional roles in many cellular processes in diverse organisms. While a number of rG4 examples have been reported in coding messenger RNAs (mRNA), so far only limited works have studied rG4s in non-coding RNAs (ncRNAs), especially in long non-coding RNAs (lncRNAs) that are of emerging interest and significance in biology. Herein, we report that MALAT1 lncRNA contains conserved rG4 motifs, forming thermostable rG4 structures with parallel topology. We also show that rG4s in MALAT1 lncRNA can interact with NONO protein with high specificity and affinity in vitro and in nuclear cell lysate, and we provide in vivo data to support that NONO protein recognizes MALAT1 lncRNA via rG4 motifs. Notably, we demonstrate that rG4s in MALAT1 lncRNA can be targeted by rG4-specific small molecule, peptide, and L-aptamer, leading to the dissociation of MALAT1 rG4-NONO protein interaction. Altogether, this study uncovers new and important rG4s in MALAT1 lncRNAs, reveals their specific interactions with NONO protein, offers multiple strategies for targeting MALAT1 and its RNA-protein complex via its rG4 structure, and illustrates the prevalence and significance of rG4s in ncRNAs.

DEGRADATION OF MESSENGER RNA IN MAMMALIAN CELLS

1972 ◽  
Vol 71 (2_Suppla) ◽  
pp. S369-S380 ◽  
Author(s):  
Francis T. Kenney ◽  
Kai-Lin Lee ◽  
Charles D. Stiles
Keyword(s):  
Messenger Rna ◽  
Mammalian Cells ◽  
Messenger Rnas ◽  
Tyrosine Transaminase

ABSTRACT Analyses of the response of hydrocortisone-induced tyrosine transaminase in cultured H-35 cells to inhibitors of translation (cycloheximide, puromycin) suggest: (1) that bound ribosomes stabilize messenger RNA in vivo; (2) that messenger is degraded at a rate determined by the rate of translation. Since specific messenger RNAs of mammalian cells are degraded at quite different rates, there may be extensive heterogeneity either in the rate at which ribosomes traverse different messengers or in the number of ribosomes which translate specific messenger RNAs.

The Role of microRNAs in the Viral Infections

2019 ◽  
Vol 24 (39) ◽  
pp. 4659-4667 ◽  
Author(s):  
Mona Fani ◽  
Milad Zandi ◽  
Majid Rezayi ◽  
Nastaran Khodadad ◽  
Hadis Langari ◽  
...  
Keyword(s):  
Viral Infections ◽  
Rna Viruses ◽  
Regulation Of Gene Expression ◽  
Molecular Structures ◽  
Main Function ◽  
Cellular Functions ◽  
Viral Genes ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs) are non-coding RNAs with 19 to 24 nucleotides which are evolutionally conserved. MicroRNAs play a regulatory role in many cellular functions such as immune mechanisms, apoptosis, and tumorigenesis. The main function of miRNAs is the post-transcriptional regulation of gene expression via mRNA degradation or inhibition of translation. In fact, many of them act as an oncogene or tumor suppressor. These molecular structures participate in many physiological and pathological processes of the cell. The virus can also produce them for developing its pathogenic processes. It was initially thought that viruses without nuclear replication cycle such as Poxviridae and RNA viruses can not code miRNA, but recently, it has been proven that RNA viruses can also produce miRNA. The aim of this articles is to describe viral miRNAs biogenesis and their effects on cellular and viral genes.

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