A U1i RNA that Enhances HIV-1 RNA Splicing with an Elongated Recognition Domain Is an Optimal Candidate for Combination HIV-1 Gene Therapy

Corpo, Olivier Del; Goguen, Ryan P.; Malard, Camille M.G.; Daher, Aı̈cha; Colby-Germinario, Susan P.; Scarborough, Robert J.; Gatignol, Anne

doi:10.1016/j.omtn.2019.10.011

Cited by 14 publications

(10 citation statements)

References 64 publications

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“…One example is targeting of the U1 snRNA by U1 interference RNAs. These U1i RNAs are designed to interfere with polyadenylation or enhance splicing of HIV-1 RNA, and they are able to efficiently inhibit HIV-1 replication ( Del Corpo et al., 2019 ). As well, antisense RNA sequences can be found in the form of peptide-nucleotide fused molecules, in which the antisense RNA is fused to a protein involved in splicing regulation or inhibition.…”

Section: Therapeutic Targeting Of Hiv-1 Rna Metabolism Pathwaysmentioning

confidence: 99%

HibeRNAtion: HIV-1 RNA Metabolism and Viral Latency

Crespo

Rao

Mahmoudi

2022

Front. Cell. Infect. Microbiol.

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HIV-1 infection remains non-curative due to the latent reservoir, primarily a small pool of resting memory CD4+ T cells bearing replication-competent provirus. Pharmacological reversal of HIV-1 latency followed by intrinsic or extrinsic cell killing has been proposed as a promising strategy to target and eliminate HIV-1 viral reservoirs. Latency reversing agents have been extensively studied for their role in reactivating HIV-1 transcription in vivo, although no permanent reduction of the viral reservoir has been observed thus far. This is partly due to the complex nature of latency, which involves strict intrinsic regulation at multiple levels at transcription and RNA processing. Still, the molecular mechanisms that control HIV-1 latency establishment and maintenance have been almost exclusively studied in the context of chromatin remodeling, transcription initiation and elongation and most known LRAs target LTR-driven transcription by manipulating these. RNA metabolism is a largely understudies but critical mechanistic step in HIV-1 gene expression and latency. In this review we provide an update on current knowledge on the role of RNA processing mechanisms in viral gene expression and latency and speculate on the possible manipulation of these pathways as a therapeutic target for future cure studies.

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Section: Therapeutic Targeting Of Hiv-1 Rna Metabolism Pathwaysmentioning

confidence: 99%

HibeRNAtion: HIV-1 RNA Metabolism and Viral Latency

Crespo

Rao

Mahmoudi

2022

Front. Cell. Infect. Microbiol.

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“…68 However, tumors occur when cancer cells escape the immune system by creating an immunosuppressive environment. [69][70][71][72] Therefore, the focus of recent research has shifted from targeted therapy to immunotherapy, hoping to be used to treat more patients with cancer. This is as a result of immune escape being common for all tumors, and restoring the immune system can help destroy tumors.…”

Section: Next-generation Sequencing and Immunotherapy For Tumorsmentioning

confidence: 99%

Power and Promise of Next-Generation Sequencing in Liquid Biopsies and Cancer Control

Liu

et al. 2020

Cancer Control

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Traditional methods of cancer treatment are usually based on the morphological and histological diagnosis of tumors, and they are not optimized according to the specific situation. Precision medicine adjusts the existing treatment regimen based on the patient’s genomic information to make it most suitable for patients. Detection of genetic mutations in tumors is the basis of precise cancer medicine. Through the analysis of genetic mutations in patients with cancer, we can tailor the treatment plan for each patient with cancer to maximize the curative effect, minimize damage to healthy tissues, and optimize resources. In recent years, next-generation sequencing technology has developed rapidly and has become the core technology of precise targeted therapy and immunotherapy for cancer. From early cancer screening to treatment guidance for patients with advanced cancer, liquid biopsy is increasingly used in cancer management. This is as a result of the development of better noninvasive, repeatable, sensitive, and accurate tools used in early screening, diagnosis, evaluation, and monitoring of patients. Cell-free DNA, which is a new noninvasive molecular pathological detection method, often carries tumor-specific gene changes. It plays an important role in optimizing treatment and evaluating the efficacy of different treatment options in clinical trials, and it has broad clinical applications.

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“…RNA isolated from transfected Neuro-2A cells at 48 hours was obtained in triplicates as well. The RNA extraction was carried out using TRIzol reagent (Invitrogen) and precipitated with anhydrous ethanol as described [ 50 , 55 ]. Total RNA resuspended in Ultrapure DNase/RNase-free distilled water (Invitrogen) was purified through miRNeasy mini kit columns (QIAGEN).…”

Section: Methodsmentioning

confidence: 99%

Profound downregulation of neural transcription factor Npas4 and Nr4a family in fetal mice neurons infected with Zika virus

et al. 2021

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Zika virus (ZIKV) infection of neurons leads to neurological complications and congenital malformations of the brain of neonates. To date, ZIKV mechanism of infection and pathogenesis is not entirely understood and different studies on gene regulation of ZIKV-infected cells have identified a dysregulation of inflammatory and stem cell maintenance pathways. MicroRNAs (miRNAs) are post-transcriptional regulators of cellular genes and they contribute to cell development in normal function and disease. Previous reports with integrative analyses of messenger RNAs (mRNAs) and miRNAs during ZIKV infection have not identified neurological pathway defects. We hypothesized that dysregulation of pathways involved in neurological functions will be identified by RNA profiling of ZIKV-infected fetal neurons. We therefore used microarrays to analyze gene expression levels following ZIKV infection of fetal murine neurons. We observed that the expression levels of transcription factors such as neural PAS domain protein 4 (Npas4) and of three members of the orphan nuclear receptor 4 (Nr4a) were severely decreased after viral infection. We confirmed that their downregulation was at both the mRNA level and at the protein level. The dysregulation of these transcription factors has been previously linked to aberrant neural functions and development. We next examined the miRNA expression profile in infected primary murine neurons by microarray and found that various miRNAs were dysregulated upon ZIKV infection. An integrative analysis of the differentially expressed miRNAs and mRNAs indicated that miR-7013-5p targets Nr4a3 gene. Using miRmimics, we corroborated that miR-7013-5p downregulates Nr4a3 mRNA and protein levels. Our data identify a profound dysregulation of neural transcription factors with an overexpression of miR-7013-5p that results in decreased Nr4a3 expression, likely a main contributor to ZIKV-induced neuronal dysfunction.

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A U1i RNA that Enhances HIV-1 RNA Splicing with an Elongated Recognition Domain Is an Optimal Candidate for Combination HIV-1 Gene Therapy

Cited by 14 publications

References 64 publications

HibeRNAtion: HIV-1 RNA Metabolism and Viral Latency

HibeRNAtion: HIV-1 RNA Metabolism and Viral Latency

Power and Promise of Next-Generation Sequencing in Liquid Biopsies and Cancer Control

Profound downregulation of neural transcription factor Npas4 and Nr4a family in fetal mice neurons infected with Zika virus

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