scholarly journals The Long Noncoding RNA HEAL Regulates HIV-1 Replication through Epigenetic Regulation of the HIV-1 Promoter

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Ti-Chun Chao ◽  
Qiong Zhang ◽  
Zhonghan Li ◽  
Shashi Kant Tiwari ◽  
Yue Qin ◽  
...  
Keyword(s):  
T Cells ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Hiv Replication ◽  
Genome Wide ◽  
Primary Monocyte ◽  
A Genome ◽  
Hiv 1

ABSTRACT A major challenge in finding a cure for HIV-1/AIDS is the difficulty in identifying and eradicating persistent reservoirs of replication-competent provirus. Long noncoding RNAs (lncRNAs, >200 nucleotides) are increasingly recognized to play important roles in pathophysiology. Here, we report the first genome-wide expression analysis of lncRNAs in HIV-1-infected primary monocyte-derived macrophages (MDMs). We identified an lncRNA, which we named HIV-1-enhanced lncRNA (HEAL), that is upregulated by HIV-1 infection of MDMs, microglia, and T lymphocytes. Peripheral blood mononuclear cells of HIV-1-infected individuals show elevated levels of HEAL. Importantly, HEAL is a broad enhancer of multiple HIV-1 strains because depletion of HEAL inhibited X4, R5, and dual-tropic HIV replications and the inhibition was rescued by HEAL overexpression. HEAL forms a complex with the RNA-binding protein FUS, which facilitates HIV replication through at least two mechanisms: (i) HEAL-FUS complex binds the HIV promoter and enhances recruitment of the histone acetyltransferase p300, which positively regulates HIV transcription by increasing histone H3K27 acetylation and P-TEFb enrichment on the HIV promoter, and (ii) HEAL-FUS complex is enriched at the promoter of the cyclin-dependent kinase 2 gene, CDK2, to enhance CDK2 expression. Notably, HEAL knockdown and knockout mediated by RNA interference (RNAi) and CRISPR-Cas9, respectively, prevent HIV-1 recrudescence in T cells and microglia upon cessation of azidothymidine treatment in vitro. Our results suggest that silencing of HEAL or perturbation of the HEAL-FUS ribonucleoprotein complex could provide a new epigenetic silencing strategy to eradicate viral reservoirs and effect a cure for HIV-1/AIDS. IMPORTANCE Despite our increased understanding of the functions of lncRNAs, their potential to develop HIV/AIDS cure strategies remains unexplored. A genome-wide analysis of lncRNAs in HIV-1-infected primary monocyte-derived macrophages (MDMs) was performed, and 1,145 differentially expressed lncRNAs were identified. An lncRNA named HIV-1-enhanced lncRNA (HEAL) is upregulated by HIV-1 infection and promotes HIV replication in T cells and macrophages. HEAL forms a complex with the RNA-binding protein FUS to enhance transcriptional coactivator p300 recruitment to the HIV promoter. Furthermore, HEAL knockdown and knockout prevent HIV-1 recrudescence in T cells and microglia upon cessation of azidothymidine treatment, suggesting HEAL as a potential therapeutic target to cure HIV-1/AIDS.

scholarly journals A genome-wide homologous recombination screen identifies the RNA-binding protein RBMX as a component of the DNA-damage response

2012 ◽  
Vol 14 (3) ◽  
pp. 318-328 ◽  
Author(s):  
Britt Adamson ◽  
Agata Smogorzewska ◽  
Frederic D. Sigoillot ◽  
Randall W. King ◽  
Stephen J. Elledge
Keyword(s):  
Dna Damage ◽  
Homologous Recombination ◽  
Dna Damage Response ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Genome Wide ◽  
A Genome ◽  
Damage Response

scholarly journals RNA-binding protein hnRNPLL regulates mRNA splicing and stability during B-cell to plasma-cell differentiation

2015 ◽  
Vol 112 (15) ◽  
pp. E1888-E1897 ◽  
Author(s):  
Xing Chang ◽  
Bin Li ◽  
Anjana Rao
Keyword(s):  
Cell Differentiation ◽  
B Cell ◽  
Plasma Cell ◽  
Rna Binding ◽  
Plasma Cells ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Plasma Cell Differentiation ◽  
Genome Wide ◽  
A Genome

Posttranscriptional regulation is a major mechanism to rewire transcriptomes during differentiation. Heterogeneous nuclear RNA-binding protein LL (hnRNPLL) is specifically induced in terminally differentiated lymphocytes, including effector T cells and plasma cells. To study the molecular functions of hnRNPLL at a genome-wide level, we identified hnRNPLL RNA targets and binding sites in plasma cells through integrated Photoactivatable-Ribonucleoside-Enhanced Cross-Linking and Immunoprecipitation (PAR-CLIP) and RNA sequencing. hnRNPLL preferentially recognizes CA dinucleotide-containing sequences in introns and 3′ untranslated regions (UTRs), promotes exon inclusion or exclusion in a context-dependent manner, and stabilizes mRNA when associated with 3′ UTRs. During differentiation of primary B cells to plasma cells, hnRNPLL mediates a genome-wide switch of RNA processing, resulting in loss of B-cell lymphoma 6 (Bcl6) expression and increased Ig production—both hallmarks of plasma-cell maturation. Our data identify previously unknown functions of hnRNPLL in B-cell to plasma-cell differentiation and demonstrate that the RNA-binding protein hnRNPLL has a critical role in tuning transcriptomes of terminally differentiating B lymphocytes.

Abstract 362: Genomewide Assessment of Posttranscriptional Events Orchestrated by Quaking that Determine Monocyte Fate

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Eric P van der Veer
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Cellular Adhesion ◽  
Growth And Survival ◽  
Expression Levels ◽  
Protein Levels ◽  
Atherosclerotic Lesions ◽  
Genome Wide ◽  
A Genome

The post-transcriptional events that enable monocytes to home to sites of vascular injury, and subsequently differentiate into macrophages within atherosclerotic lesions are poorly understood. We discovered that the mRNA and protein levels of the RNA-binding protein Quaking (QKI) are augmented in CD14+ myeloid cells extracted from advanced human atherosclerotic plaques (4.2-fold upregulated vs. early lesions; p<0.01). This prompted us to investigate how the RNA-binding properties of QKI could influence monocyte fate. Our approach was to examine, at a genome-wide level, how altering the expression levels of QKI could impact pre-mRNA splicing, expression, and localization upon differentiation of human monocytes into Mf. For this, we employed both array-based gene expression analyses as well as next-generation sequencing techniques (RNA-seq) of THP-1 monocytic cells as well as CD14+ monocytes derived from the peripheral blood of a unique, QKI haploinsufficient subject (with sibling control). Despite low expression levels of QKI in monocytes, the abrogation of QKI in these cells perturbed cellular adhesion and the ensuing establishment of the cytoskeletal architecture. Interestingly, our investigation of post-transcriptional events that are associated with the conversion of the monocyte to a macrophage, uncovered: 1) 536 alternative splicing events (p<0.05) that are directly mediated by binding of QKI proximal to the splice site (QBS)(Fig. 1A); and 2) 1214 differentially expressed genes (minimally +/- 1.5-fold; p<0.05) that indicate that QKI modulates monocyte activation and differentiation by regulating inflammation, cell growth and survival, RNA editing and lipid metabolism via activation of the LXR/RXR pathway (Fig. 1B). Collectively, our data illustrate the post-transcriptional events that drive monocyte to macrophage differentiation, and identify the RNA-binding protein QKI as an orchestrator of this inflammatory response.

scholarly journals Genome-wide landscape of RNA-binding protein target site dysregulation reveals a major impact on psychiatric disorder risk

2021 ◽  
Vol 53 (2) ◽  
pp. 166-173
Author(s):  
Christopher Y. Park ◽  
Jian Zhou ◽  
Aaron K. Wong ◽  
Kathleen M. Chen ◽  
Chandra L. Theesfeld ◽  
...  
Keyword(s):  
Psychiatric Disorder ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Target Site ◽  
Protein Target ◽  
Genome Wide ◽  
Disorder Risk

scholarly journals Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR

Science ◽  
1991 ◽  
Vol 251 (5001) ◽  
pp. 1597-1600 ◽  
Author(s):  
A Gatignol ◽  
A Buckler-White ◽  
B Berkhout ◽  
K. Jeang
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Tar Rna ◽  
Hiv 1

scholarly journals Genome-wide identification and expression analysis of glycine-rich RNA-binding protein family in sweet potato wild relative Ipomoea trifida

Gene ◽  
2019 ◽  
Vol 686 ◽  
pp. 177-186 ◽  
Author(s):  
Yan Lu ◽  
Jian Sun ◽  
Zhengmei Yang ◽  
Chenxu Zhao ◽  
Mingku Zhu ◽  
...  
Keyword(s):  
Sweet Potato ◽  
Expression Analysis ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Protein Family ◽  
Wild Relative ◽  
Ipomoea Trifida ◽  
Genome Wide

Inhibition of Rev-mediated HIV-1 expression by an RNA binding protein encoded by the interferon-inducible 9-27 gene

Science ◽  
1993 ◽  
Vol 259 (5099) ◽  
pp. 1314-1318 ◽  
Author(s):  
P Constantoulakis ◽  
M Campbell ◽  
B. Felber ◽  
G Nasioulas ◽  
E Afonina ◽  
...  
Keyword(s):  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Hiv 1

Role of the RNA-binding protein HuR in posttranscriptional regulation of IL-13 in T cells

2007 ◽  
Vol &NA; ◽  
pp. S35
Author(s):  
Cristiana Stellato ◽  
J Fang ◽  
B Tancowny ◽  
J Fan ◽  
F Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Posttranscriptional Regulation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein

scholarly journals HIV-1 TAR RNA Subverts RNA Interference in Transfected Cells through Sequestration of TAR RNA-binding Protein, TRBP

2006 ◽  
Vol 281 (38) ◽  
pp. 27674-27678 ◽  
Author(s):  
Yamina Bennasser ◽  
Man Lung Yeung ◽  
Kuan-Teh Jeang
Keyword(s):  
Rna Interference ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Transfected Cells ◽  
Tar Rna ◽  
Hiv 1
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