Interactions of host miRNAs in the flavivirus 3´UTR genome: From bioinformatics predictions to practical approaches

Avila-Bonilla, Rodolfo Gamaliel; Salas-Benito, Juan Santiago

doi:10.3389/fcimb.2022.976843

Cited by 6 publications

(2 citation statements)

References 131 publications

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“…As reported, JMTV retained the 5′-CAAGUG-3′ sequence in the UTR of all the segments during its first isolation, which indicated that all four segments belonged to the same virus [ 2 ]. The conserved location of the 5′-CAAGUG-3′ sequence in the first structures of the untranslated regions may indicate that this region is involved in interactions with viral and/or cellular proteins to regulate the virus’s life cycle, similarly to how it occurs in other viruses of the Orthoflavivirus genus [ 34 , 35 , 36 , 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Untranslated Regions of a Segmented Kindia Tick Virus Genome Are Highly Conserved and Contain Multiple Regulatory Elements for Viral Replication

Tsishevskaya,

Alkhireenko,

Bayandin

et al. 2024

Microorganisms

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Novel segmented tick-borne RNA viruses belonging to the group of Jingmenviruses (JMVs) are widespread across Africa, Asia, Europe, and America. In this work, we obtained whole-genome sequences of two Kindia tick virus (KITV) isolates and performed modeling and the functional annotation of the secondary structure of 5′ and 3′ UTRs from JMV and KITV viruses. UTRs of various KITV segments are characterized by the following points: (1) the polyadenylated 3′ UTR; (2) 5′ DAR and 3′ DAR motifs; (3) a highly conserved 5′-CACAG-3′ pentanucleotide; (4) a binding site of the La protein; (5) multiple UAG sites providing interactions with the MSI1 protein; (6) three homologous sequences in the 5′ UTR and 3′ UTR of segment 2; (7) the segment 2 3′ UTR of a KITV/2017/1 isolate, which comprises two consecutive 40 nucleotide repeats forming a Y-3 structure; (8) a 35-nucleotide deletion in the second repeat of the segment 2 3′ UTR of KITV/2018/1 and KITV/2018/2 isolates, leading to a modification of the Y-3 structure; (9) two pseudoknots in the segment 2 3′ UTR; (10) the 5′ UTR and 3′ UTR being represented by patterns of conserved motifs; (11) the 5′-CAAGUG-3′ sequence occurring in early UTR hairpins. Thus, we identified regulatory elements in the UTRs of KITV, which are characteristic of orthoflaviviruses. This suggests that they hold functional significance for the replication of JMVs and the evolutionary similarity between orthoflaviviruses and segmented flavi-like viruses.

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Section: Discussionmentioning

confidence: 99%

Untranslated Regions of a Segmented Kindia Tick Virus Genome Are Highly Conserved and Contain Multiple Regulatory Elements for Viral Replication

Tsishevskaya,

Alkhireenko,

Bayandin

et al. 2024

Microorganisms

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“…This new type of vaccines can induce neutralizing antibody production in mice [268] and could be a promising strategy to avoid the antibody-dependent enhancement (ADE) phenomenon, which causes increased viral replication due to the production of specific antibodies against viruses that facilitates viral entry, upregulates autophagy, and inhibits interferon signaling. For some viruses, the ADE phenomenon is not abolished with MREbased vaccines, but this question could be overcome by proposing miRNAs not as a viral genome modification, but as an active compound of a drug used as prevention or therapeutic treatment, as shown in a recent review [269].…”

Section: Artificial Micrornasmentioning

confidence: 99%

Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview

Diani,

Lagni,

Lotti

et al. 2023

Microorganisms

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Flaviviruses cause numerous pathologies in humans across a broad clinical spectrum with potentially severe clinical manifestations, including hemorrhagic and neurological disorders. Among human flaviviruses, some viral proteins show high conservation and are good candidates as targets for drug design. From an epidemiological point of view, flaviviruses cause more than 400 million cases of infection worldwide each year. In particular, the Yellow Fever, dengue, West Nile, and Zika viruses have high morbidity and mortality—about an estimated 20,000 deaths per year. As they depend on human vectors, they have expanded their geographical range in recent years due to altered climatic and social conditions. Despite these epidemiological and clinical premises, there are limited antiviral treatments for these infections. In this review, we describe the major compounds that are currently under evaluation for the treatment of flavivirus infections and the challenges faced during clinical trials, outlining their mechanisms of action in order to present an overview of ongoing studies. According to our review, the absence of approved antivirals for flaviviruses led to in vitro and in vivo experiments aimed at identifying compounds that can interfere with one or more viral cycle steps. Still, the currently unavailability of approved antivirals poses a significant public health issue.

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Identification of miR-192 target genes in porcine endometrial epithelial cells based on miRNA pull-down

Gao

Chen

et al. 2023

Mol Biol Rep

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MicroRNAs (miRNAs)-a class of small endogenous non-coding RNAs-are widely involved in posttranscriptional gene regulation of numerous physiological processes. High-throughput sequencing revealed that the miR-192 expression level appeared to be signi cantly higher in the blood exosomes of sows at early gestation than that in non-pregnant sows. Furthermore, miR-192 was hypothesized to have a regulatory role in embryo implantation; however, the target genes involved in exerting the regulatory function of miR-192 required further elucidation.Methods: In the present study, potential target genes of miR-192 in porcine endometrial epithelial cells (PEECs) were identi ed through biotin-labeled miRNA pull-down; functional and pathway enrichment analysis was performed via gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Bioinformatic analyses were concurrently used to predict the potential target genes associated with sow embryo implantation. In addition, double luciferase reporter vectors, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and Western blot were performed to verify the targeting and regulatory roles of the abovementioned target genes.Results: A total of 1688 differentially expressed mRNAs were identi ed via miRNA pull-down. Through RT-qPCR, the accuracy of the sequencing data was veri ed. In the bioinformatics analysis, potential target genes of miR-192 appeared to form a dense inter-regulatory network and regulated multiple signaling pathways, such as metabolic pathways and the PI3K-Akt, MAPKs, and mTOR signaling pathways, that are relevant to the mammalian embryo implantation process. In addition, CSK (C-terminal Src kinase) and YY1 (Yin-Yang-1) were predicted to be potential candidates, and we validated that miR-192 directly targets and suppresses the expression of the CSK and YY1 genes.Conclusion: We screened 1688 potential target genes of miR-192 were screened, and CSK and YY1 were identi ed as miR-192 target genes. The outcomes of the present study provide novel insights into the regulatory mechanism of porcine embryo implantation and the identi cation of miRNA target genes.

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Interactions of host miRNAs in the flavivirus 3´UTR genome: From bioinformatics predictions to practical approaches

Cited by 6 publications

References 131 publications

Untranslated Regions of a Segmented Kindia Tick Virus Genome Are Highly Conserved and Contain Multiple Regulatory Elements for Viral Replication

Untranslated Regions of a Segmented Kindia Tick Virus Genome Are Highly Conserved and Contain Multiple Regulatory Elements for Viral Replication

Vector-Transmitted Flaviviruses: An Antiviral Molecules Overview

Identification of miR-192 target genes in porcine endometrial epithelial cells based on miRNA pull-down

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